The school of nature I. transmembrane signaling

Self/Nonself - Immune Recognition and Signaling

Volumn 1, Issue 1, 2010, Pages 4-39

  Sigalov, Alexander B ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

B cell activation; B cell receptor; BCR; Cell activation; Cytoplasmic homointeractions; Fc receptors; Glycoprotein VI; GPVI; Immune signaling; Immunoreceptor tyrosine based activation motif; Intrinsically disordered proteins; ITAM; Ligand receptor complex lifetime; Mechanistic model; Mirr; Multichain immune recognition receptors; Natural killer cell receptors; NK receptors; Platelet collagen receptor; Protein protein interactions; Receptor clustering; Receptor orientation; Receptor tyrosine kinases; SCHOOL model; Signal propagation; Signaling chain homooligomerization model; T cell activation; T cell receptor; TCR; Transmembrane interactions; TREM; Triggering receptors expressed on myeloid cells

Indexed keywords

B LYMPHOCYTE RECEPTOR; CELL SURFACE RECEPTOR; FC RECEPTOR; GLYCOPROTEIN VI; NATURAL KILLER CELL RECEPTOR NKG2D; T LYMPHOCYTE RECEPTOR;

ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BIOCHEMISTRY; CYTOLOGY; CYTOPLASM; IMMUNOLOGY; LIGAND BINDING; MOLECULAR BIOLOGY; MOLECULAR RECOGNITION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; VIROLOGY;

EID: 77956288834     PISSN: 19382030     EISSN: 19382049     Source Type: Journal    
DOI: 10.4161/self.1.1.10832     Document Type: Article

References (392)

1. Rudd CE. Disabled receptor signaling and new primary immunodeficiency disorders. N Engl J Med 2006; 354:1874-1877.
2. Sigalov AB, ed. Multichain Immune Recognition Receptor Signaling: From Spatiotemporal Organization to Human Disease. New York: Springer-Verlag 2008.
3. Keegan AD, Paul WE. Multichain immune recognition receptors: similarities in structure and signaling pathways. Immunol Today 1992; 13:63-68.
4. Sigalov AB. Immune cell signaling: a novel mechanistic model reveals new therapeutic targets. Trends Pharmacol Sci 2006; 27:518-524.
5. Hubbard SR, Till JH. Protein tyrosine kinase structure and function. Annu Rev Biochem 2000; 69:373-398.
6. Zhou T, Mountz JD, Kimberly RP. Immunobiology of tumor necrosis factor receptor superfamily. Immunol Res 2002; 26:323-336.
7. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-b regulation of immune responses. Annu Rev Immunol 2006; 24:99-146.
8. Geijtenbeek TB, Gringhuis SI. Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 2009; 9:465-479.
9. Krogsgaard M, Davis MM. How T cells 'see' antigen. Nat Immunol 2005; 6:239-245.
10. DeFranco AL. B-cell activation 2000. Immunol Rev 2000; 176:5-9.
11. Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J. B cell antigen receptor signaling 101. Mol Immunol 2004; 41:599-613.
12. Takai T. Fc receptors and their role in immune regulation and autoimmunity. J Clin Immunol 2005; 25:1-18.
13. Takai T. Fc receptors: their diverse functions in immunity and immune disorders. Springer Semin Immunopathol 2006; 28:303-304.
14. Colonna M, Nakajima H, Navarro F, Lopez-Botet M. A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells. J Leukoc Biol 1999; 66:375-381.
15. Borrego F, Kabat J, Kim DK, Lieto L, Maasho K, Pena J, et al. Structure and function of major histocompatibility complex (MHC) class I specific receptors expressed on human natural killer (NK) cells. Mol Immunol 2002; 38:637-660.
16. Moroi M, Jung SM. Platelet glycoprotein VI: its structure and function. Thromb Res 2004; 114:221-233.
17. Barclay AN, Brown MH. The SIRP family of receptors and immune regulation. Nat Rev Immunol 2006; 6:457-464.
18. Kanazawa N, Tashiro K, Miyachi Y. Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin- 2 and BDCA-2. Immunobiology 2004; 209:179-190.
19. Biassoni R, Cantoni C, Falco M, Pende D, Millo R, Moretta L, et al. Human natural killer cell activating receptors. Mol Immunol 2000; 37:1015-1024.
20. Biassoni R, Cantoni C, Marras D, Giron-Michel J, Falco M, Moretta L, et al. Human natural killer cell receptors: insights into their molecular function and structure. J Cell Mol Med 2003; 7:376-387.
21. Aoki N, Kimura S, Xing Z. Role of DAP12 in innate and adaptive immune responses. Curr Pharm Des 2003; 9:7-10.
22. Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc Natl Acad Sci USA 1999; 96:9792-9796.
23. van den Berg TK, Yoder JA, Litman GW. On the origins of adaptive immunity: innate immune receptors join the tale. Trends Immunol 2004; 25:11-16.
24. Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266-1273.
25. Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology 2005; 115:433-440.
26. Nakahashi C, Tahara-Hanaoka S, Totsuka N, Okoshi Y, Takai T, Ohkohchi N, et al. Dual assemblies of an activating immune receptor, MAIR-II, with ITAMbearing adapters DAP12 and FcRgamma chain on peritoneal macrophages. J Immunol 2007; 178:765-770.
27. Fujimoto M, Takatsu H, Ohno H. CMRF-35-like molecule-5 constitutes novel paired receptors, with CMRF-35-like molecule-1, to transduce activation signal upon association with FcRg. Int Immunol 2006; 18:1499-1508.
28. Stewart CA, Vivier E, Colonna M. Strategies of natural killer cell recognition and signaling. Curr Top Microbiol Immunol 2006; 298:1-21.
29. Reth M. Antigen receptor tail clue. Nature 1989; 338:383-384.
30. Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, et al. SH2 domains recognize specific phosphopeptide sequences. Cell 1993; 72:767-778.
31. Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med 2000; 192:1059-1068.
32. Manolios N, Bonifacino JS, Klausner RD. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science 1990; 249:274-277.
33. Call ME, Pyrdol J, Wiedmann M, Wucherpfennig KW. The organizing principle in the formation of the T cell receptor-CD3 complex. Cell 2002; 111:967-979.
34. Michnoff CH, Parikh VS, Lelsz DL, Tucker PW. Mutations within the NH2-terminal transmembrane domain of membrane immunoglobulin (Ig) M alters Ig-a and Ig-b association and signal transduction. J Biol Chem 1994; 269:24237-24244.
35. Daeron M. Fc receptor biology. Annu Rev Immunol 1997; 15:203-234.
36. Feng J, Garrity D, Call ME, Moffett H, Wucherpfennig KW. Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors. Immunity 2005; 22:427-438.
37. Feng J, Call ME, Wucherpfennig KW. The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site. PLoS Biol 2006; 4:142.
38. Bakema JE, de Haij S, den Hartog-Jager CF, Bakker J, Vidarsson G, van Egmond M, et al. Signaling through mutants of the IgA receptor CD89 and consequences for Fc receptor g-chain interaction. J Immunol 2006; 176:3603-3610.
39. Varin-Blank N, Metzger H. Surface expression of mutated subunits of the high affinity mast cell receptor for IgE. J Biol Chem 1990; 265:15685-15694.
40. Stevens TL, Blum JH, Foy SP, Matsuuchi L, DeFranco AL. A mutation of the mu transmembrane that disrupts endoplasmic reticulum retention. Effects on association with accessory proteins and signal transduction. J Immunol 1994; 152:4397-4406.
41. Zidovetzki R, Rost B, Pecht I. Role of transmembrane domains in the functions of B- and T-cell receptors. Immunol Lett 1998; 64:97-107.
42. Blum JH, Stevens TL, DeFranco AL. Role of the mu immunoglobulin heavy chain transmembran and cytoplasmic domains in B cell antigen receptor expression and signal transduction. J Biol Chem 1993; 268:27236-27245.
43. Ra C, Jouvin MH, Kinet JP. Complete structure of the mouse mast cell receptor for IgE (FcepsilonRI) and surface expression of chimeric receptors (ratmouse- human) on transfected cells. J Biol Chem 1989; 264:15323-15327.
44. Sigalov AB. Protein intrinsic disorder and oligomericity in cell signaling. Mol Biosyst 2010; DOI: 10.1039/B916030M.
45. Heldin CH. Dimerization of cell surface receptors in signal transduction. Cell 1995; 80:213-223.
46. Metzger H. Transmembrane signaling: the joy of aggregation. J Immunol 1992; 149:1477-1487.
47. Lemmon MA, Schlessinger J. Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 1994; 19:459-463.
48. Klemm JD, Schreiber SL, Crabtree GR. Dimerization as a regulatory mechanism in signal transduction. Annu Rev Immunol 1998; 16:569-592.
49. Sigalov AB. Multichain immune recognition receptor signaling: different players, same game? Trends Immunol 2004; 25:583-589.
50. Cooper JA, Qian H. A mechanism for SRC kinasedependent signaling by noncatalytic receptors. Biochemistry 2008; 47:5681-5688.
51. Weiss A, Schlessinger J. Switching signals on or off by receptor dimerization. Cell 1998; 94:277-280.
52. Boniface JJ, Rabinowitz JD, Wulfing C, Hampl J, Reich Z, Altman JD, et al. Initiation of signal transduction through the T cell receptor requires the multivalent engagement of peptide/MHC ligands. Immunity 1998; 9:459-466.
53. Holowka D, Baird B. Antigen-mediated IGE receptor aggregation and signaling: a window on cell surface structure and dynamics. Annu Rev Biophys Biomol Struct 1996; 25:79-112.
54. Thyagarajan R, Arunkumar N, Song W. Polyvalent antigens stabilize B cell antigen receptor surface signaling microdomains. J Immunol 2003; 170:6099-6106.
55. Bankovich AJ, Raunser S, Juo ZS, Walz T, Davis MM, Garcia KC. Structural insight into pre-B cell receptor function. Science 2007; 316:291-294.
56. Puffer EB, Pontrello JK, Hollenbeck JJ, Kink JA, Kiessling LL. Activating B cell signaling with defined multivalent ligands. ACS Chem Biol 2007; 2:252-262.
57. Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, et al. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat Immunol 2007; 8:398-408.
58. Adams EJ, Chien YH, Garcia KC. Structure of a gd T cell receptor in complex with the nonclassical MHC T22. Science 2005; 308:227-231.
59. Bachmann MF, Ohashi PS. The role of T-cell receptor dimerization in T-cell activation. Immunol Today 1999; 20:568-576.
60. Bachmann MF, Salzmann M, Oxenius A, Ohashi PS. Formation of TCR dimers/trimers as a crucial step for T cell activation. Eur J Immunol 1998; 28:2571-2579.
61. DeFranco AL, Gold MR, Jakway JP. B-lymphocyte signal transduction in response to anti-immunoglobulin and bacterial lipopolysaccharide. Immunol Rev 1987; 95:161-176.
62. Posner RG, Savage PB, Peters AS, Macias A, DelGado J, Zwartz G, et al. A quantitative approach for studying IgE-FceRI aggregation. Mol Immunol 2002; 38:1221-1228.
63. Draberova L, Lebduska P, Halova I, Tolar P, Stokrova J, Tolarova H, et al. Signaling assemblies formed in mast cells activated via Fce receptor I dimers. Eur J Immunol 2004; 34:2209-2219.
64. Horii K, Kahn ML, Herr AB. Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI. Blood 2006; 108:936-42.
65. Cochran JR, Cameron TO, Stern LJ. The relationship of MHC-peptide binding and T cell activation probed using chemically defined MHC class II oligomers. Immunity 2000; 12:241-50.
66. Fahmy TM, Bieler JG, Schneck JP. Probing T cell membrane organization using dimeric MHC-Ig complexes. J Immunol Methods 2002; 268:93-106.
67. Kiessling LL, Gestwicki JE, Strong LE. Synthetic multivalent ligands as probes of signal transduction. Angew Chem Int Ed Engl 2006; 45:2348-68.
68. Garrity D, Call ME, Feng J, Wucherpfennig KW. The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Proc Natl Acad Sci USA 2005; 102:7641-6.
69. Radaev S, Kattah M, Rostro B, Colonna M, Sun PD. Crystal structure of the human myeloid cell activating receptor TREM-1. Structure 2003; 11:1527-35.
70. Ortega E. How do multichain immune recognition receptors signal? A structural hypothesis. Mol Immunol 1995; 32:941-5.
71. Berlanga O, Bori-Sanz T, James JR, Frampton J, Davis SJ, Tomlinson MG, et al. Glycoprotein VI oligomerization in cell lines and platelets. J Thromb Haemost 2007; 5:1026-33.
72. Symer DE, Dintzis RZ, Diamond DJ, Dintzis HM. Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays. J Exp Med 1992; 176:1421-30.
73. Schweitzer-Stenner R, Tamir I, Pecht I. Analysis of Fc(epsilon)RI-mediated mast cell stimulation by surface-carried antigens. Biophys J 1997; 72:2470-8.
74. Patrick SM, Kim S, Braunstein NS, Thomas JL, Leonard EF. Dependence of T cell activation on area of contact and density of a ligand-coated surface. J Immunol Methods 2000; 241:97-108.
75. Germain RN. T-cell signaling: the importance of receptor clustering. Curr Biol 1997; 7:640-4.
76. Alam SM, Davies GM, Lin CM, Zal T, Nasholds W, Jameson SC, et al. Qualitative and quantitative differences in T cell receptor binding of agonist and antagonist ligands. Immunity 1999; 10:227-37.
77. Cadena DL, Gill GN. Receptor tyrosine kinases. Faseb J 1992; 6:2332-7.
78. Sigalov A, Aivazian D, Stern L. Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain and of other proteins containing the immunoreceptor tyrosine-based activation motif. Biochemistry 2004; 43:2049-61.
79. Sigalov AB, Aivazian DA, Uversky VN, Stern LJ. Lipid-binding activity of intrinsically unstructured cytoplasmic domains of multichain immune recognition receptor signaling subunits. Biochemistry 2006; 45:15731-9.
80. Sigalov AB, Hendricks GM. Membrane binding mode of intrinsically disordered cytoplasmic domains of T cell receptor signaling subunits depends on lipid composition. Biochem Biophys Res Commun 2009; 389:388-93.
81. Sigalov AB, Zhuravleva AV, Orekhov VY. Binding of intrinsically disordered proteins is not necessarily accompanied by a structural transition to a folded form. Biochimie 2007; 89:419-21.
82. Mittag T, Kay LE, Forman-Kay JD. Protein dynamics and conformational disorder in molecular recognition. J Mol Recognit 2009; DOI: 10.1002/ jmr.961.
83. Tompa P, Fuxreiter M. Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem Sci 2008; 33:2-8.
84. Finger C, Escher C, Schneider D. The single transmembrane domains of human receptor tyrosine kinases encode self-interactions. Sci Signal 2009; 2:56.
85. Li E, Hristova K. Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. Biochemistry 2006; 45:6241-51.
86. Li E, You M, Hristova K. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis and forster resonance energy transfer suggest weak interactions between fibroblast growth factor receptor 3 (FGFR3) transmembrane domains in the absence of extracellular domains and ligands. Biochemistry 2005; 44:352-60.
87. Smith SO, Smith C, Shekar S, Peersen O, Ziliox M, Aimoto S. Transmembrane interactions in the activation of the Neu receptor tyrosine kinase. Biochemistry 2002; 41:9321-32.
88. Fantl WJ, Johnson DE, Williams LT. Signalling by receptor tyrosine kinases. Annu Rev Biochem 1993; 62:453-81.
89. Bormann BJ, Engelman DM. Intramembrane helixhelix association in oligomerization and transmembrane signaling. Annu Rev Biophys Biomol Struct 1992; 21:223-42.
90. Finger C, Volkmer T, Prodohl A, Otzen DE, Engelman DM, Schneider D. The stability of transmembrane helix interactions measured in a biological membrane. J Mol Biol 2006; 358:1221-8.
91. Davis MM, Boniface JJ, Reich Z, Lyons D, Hampl J, Arden B, et al. Ligand recognition by ab T cell receptors. Annu Rev Immunol 1998; 16:523-44.
92. Andersen PS, Geisler C, Buus S, Mariuzza RA, Karjalainen K. Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens. J Biol Chem 2001; 276:33452-7.
93. Garcia KC, Tallquist MD, Pease LR, Brunmark A, Scott CA, Degano M, et al. ab T cell receptor interactions with syngeneic and allogeneic ligands: affinity measurements and crystallization. Proc Natl Acad Sci USA 1997; 94:13838-43.
94. Torigoe C, Inman JK, Metzger H. An unusual mechanism for ligand antagonism. Science 1998; 281:568-72.
95. Miura Y, Takahashi T, Jung SM, Moroi M. Analysis of the interaction of platelet collagen receptor glycoprotein VI (GPVI) with collagen. A dimeric form of GPVI, but not the monomeric form, shows affinity to fibrous collagen. J Biol Chem 2002; 277:46197-204.
96. Haefner J. Modeling Biological Systems: Principles and Applications New York: Springer 2005.
97. Sigalov A. Multi-chain immune recognition receptors: spatial organization and signal transduction. Semin Immunol 2005; 17:51-64.
98. Sigalov AB. Transmembrane interactions as immunotherapeutic targets: lessons from viral pathogenesis. Adv Exp Med Biol 2007; 601:335-44.
99. Tanner KG, Kyte J. Dimerization of the extracellular domain of the receptor for epidermal growth factor containing the membrane-spanning segment in response to treatment with epidermal growth factor. J Biol Chem 1999; 274:35985-90.
100. Hubbard SR. Structural analysis of receptor tyrosine kinases. Prog Biophys Mol Biol 1999; 71:343-58.
101. Schlessinger J. Signal transduction. Autoinhibition control. Science 2003; 300:750-2.
102. Jiang G, Hunter T. Receptor signaling: when dimerization is not enough. Curr Biol 1999; 9:568-71.
103. Marianayagam NJ, Sunde M, Matthews JM. The power of two: protein dimerization in biology. Trends Biochem Sci 2004; 29:618-25.
104. Siegel RM, Muppidi JR, Sarker M, Lobito A, Jen M, Martin D, et al. SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane. J Cell Biol 2004; 167:735-44.
105. Chan FK. Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 2007; 37:101-7.
106. Chan KF, Siegel MR, Lenardo JM. Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 2000; 13:419-22.
107. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000; 103:211-25.
108. Hays JL, Watowich SJ. Oligomerization-induced modulation of TPR-MET tyrosine kinase activity. J Biol Chem 2003; 278:27456-63.
109. Hays JL, Watowich SJ. Oligomerization-dependent changes in the thermodynamic properties of the TPR-MET receptor tyrosine kinase. Biochemistry 2004; 43:10570-8.
110. Moriki T, Maruyama H, Maruyama IN. Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain. J Mol Biol 2001; 311:1011-26.
111. Yu X, Sharma KD, Takahashi T, Iwamoto R, Mekada E. Ligand-independent dimer formation of epidermal growth factor receptor (EGFR) is a step separable from ligand-induced EGFR signaling. Mol Biol Cell 2002; 13:2547-57.
112. Bell CA, Tynan JA, Hart KC, Meyer AN, Robertson SC, Donoghue DJ. Rotational coupling of the transmembrane and kinase domains of the Neu receptor tyrosine kinase. Mol Biol Cell 2000; 11:3589-99.
113. Ballinger MD, Wells JA. Will any dimer do? Nat Struct Biol 1998; 5:938-40.
114. Livnah O, Johnson DL, Stura EA, Farrell FX, Barbone FP, You Y, et al. An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation. Nat Struct Biol 1998; 5:993-1004.
115. Syed RS, Reid SW, Li C, Cheetham JC, Aoki KH, Liu B, et al. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature 1998; 395:511-6.
116. Simpson RJ, Hammacher A, Smith DK, Matthews JM, Ward LD. Interleukin-6: structure-function relationships. Protein Sci 1997; 6:929-55.
117. Greiser JS, Stross C, Heinrich PC, Behrmann I, Hermanns HM. Orientational constraints of the gp130 intracellular juxtamembrane domain for signaling. J Biol Chem 2002; 277:26959-65.
118. Muller-Newen G, Kuster A, Wijdenes J, Schaper F, Heinrich PC. Studies on the interleukin-6-type cytokine signal transducer gp130 reveal a novel mechanism of receptor activation by monoclonal antibodies. J Biol Chem 2000; 275:4579-86.
119. Autissier P, De Vos J, Liautard J, Tupitsyn N, Jacquet C, Chavdia N, et al. Dimerization and activation of the common transducing chain (gp130) of the cytokines of the IL-6 family by mAb. Int Immunol 1998; 10:1881-9.
120. Lee HK, Dunzendorfer S, Tobias PS. Cytoplasmic domain-mediated dimerizations of toll-like receptor 4 observed by b-lactamase enzyme fragment complementation. J Biol Chem 2004; 279:10564-74.
121. Weber AN, Moncrieffe MC, Gangloff M, Imler JL, Gay NJ. Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway. J Biol Chem 2005; 280:22793-9.
122. Gomes MM, Herr AB. IgA and IgA-specific receptors in human disease: structural and functional insights into pathogenesis and therapeutic potential. Springer Semin Immunopathol 2006; 28:383-95.
123. Honda Z. Fce- and Fcg-receptor signaling in diseases. Springer Semin Immunopathol 2006; 28:365-75.
124. Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 2001; 19:197-223.
125. Clemetson KJ. Platelet receptors and their role in diseases. Clin Chem Lab Med 2003; 41:253-60.
126. Reth M. Oligomeric antigen receptors: a new view on signaling for the selection of lymphocytes. Trends Immunol 2001; 22:356-60.
127. Langlet C, Bernard AM, Drevot P, He HT. Membrane rafts and signaling by the multichain immune recognition receptors. Curr Opin Immunol 2000; 12:250-5.
128. Dykstra M, Cherukuri A, Pierce SK. Rafts and synapses in the spatial organization of immune cell signaling receptors. J Leukoc Biol 2001; 70:699-707.
129. Sigalov AB. SCHOOL model and new targeting strategies. Adv Exp Med Biol 2008; 640:268-311.
130. Sigalov AB. Signaling chain homooligomerization (SCHOOL) model. Adv Exp Med Biol 2008; 640:121-63.
131. Berko D, Carmi Y, Cafri G, Ben-Zaken S, Sheikhet HM, Tzehoval E, et al. Membrane-anchored b2-microglobulin stabilizes a highly receptive state of MHC class I molecules. J Immunol 2005; 174:2116-23.
132. Pribluda VS, Pribluda C, Metzger H. Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation. Proc Natl Acad Sci USA 1994; 91:11246-50.
133. Schamel WW, Arechaga I, Risueno RM, van Santen HM, Cabezas P, Risco C, et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J Exp Med 2005; 202:493-503.
134. Jung SM, Tsuji K, Moroi M. Glycoprotein (GP) VI dimer as a major collagen-binding site of native platelets: direct evidence obtained with dimeric GPVIspecific Fabs. J Thromb Haemost 2009; 7:1347-55.
135. Pitcher LA, van Oers NS. T-cell receptor signal transmission: who gives an ITAM? Trends Immunol 2003; 24:554-60.
136. Pike KA, Baig E, Ratcliffe MJ. The avian B-cell receptor complex: distinct roles of Iga and Igb in B-cell development. Immunol Rev 2004; 197:10-25.
137. Storch B, Meixlsperger S, Jumaa H. The Ig-a ITAM is required for efficient differentiation but not proliferation of pre-B cells. Eur J Immunol 2007; 37:252-60.
138. Gazumyan A, Reichlin A, Nussenzweig MC. Igb tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization. J Exp Med 2006; 203:1785-94.
139. Lin S, Cicala C, Scharenberg AM, Kinet JP. The Fc(e)RIbeta subunit functions as an amplifier of Fc(e)RIg-mediated cell activation signals. Cell 1996; 85:985-95.
140. Sanchez-Mejorada G, Rosales C. Signal transduction by immunoglobulin Fc receptors. J Leukoc Biol 1998; 63:521-33.
141. Lysechko TL, Ostergaard HL. Differential Src family kinase activity requirements for CD3z phosphorylation/ ZAP70 recruitment and CD3e phosphorylation. J Immunol 2005; 174:7807-14.
142. Kuhns MS, Davis MM. Disruption of extracellular interactions impairs T cell receptor-CD3 complex stability and signaling. Immunity 2007; 26:357-69.
143. Chau LA, Bluestone JA, Madrenas J. Dissociation of intracellular signaling pathways in response to partial agonist ligands of the T cell receptor. J Exp Med 1998; 187:1699-709.
144. Jensen WA, Pleiman CM, Beaufils P, Wegener AM, Malissen B, Cambier JC. Qualitatively distinct signaling through T cell antigen receptor subunits. Eur J Immunol 1997; 27:707-16.
145. Pitcher LA, Mathis MA, Young JA, Deford LM, Purtic B, Wulfing C, et al. The CD3ge /de signaling module provides normal T cell functions in the absence of the TCRzeta immunoreceptor tyrosine-based activation motifs. Eur J Immunol 2005; 35:3643-54.
146. Kesti T, Ruppelt A, Wang JH, Liss M, Wagner R, Tasken K, et al. Reciprocal regulation of SH3 and SH2 domain binding via tyrosine phosphorylation of a common site in CD3{e}. J Immunol 2007; 179:878-85.
147. Chae WJ, Lee HK, Han JH, Kim SW, Bothwell AL, Morio T, et al. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor z chain ITAMs and their tyrosine residues. Int Immunol 2004; 16:1225-36.
148. Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides and coreceptors. Annu Rev Immunol 2006; 24:419-66.
149. Rojo JM, Bello R, Portoles P. T-cell receptor. Adv Exp Med Biol 2008; 640:1-11.
150. Wines BD, Trist HM, Monteiro RC, Van Kooten C, Hogarth PM. Fc receptor g chain residues at the interface of the cytoplasmic and transmembrane domains affect association with FcaRI, surface expression and function. J Biol Chem 2004; 279:26339-45.
151. Kikuchi-Maki A, Catina TL, Campbell KS. Cutting edge: KIR2DL4 transduces signals into human NK cells through association with the Fc receptor g protein. J Immunol 2005; 174:3859-63.
152. DeFranco AL, Mittelstadt PR, Blum JH, Stevens TL, Law DA, Chan VW, et al. Mechanism of B cell antigen receptor function: transmembrane signaling and triggering of apoptosis. Adv Exp Med Biol 1994; 365:9-22.
153. Morton HC, van den Herik-Oudijk IE, Vossebeld P, Snijders A, Verhoeven AJ, Capel PJ, et al. Functional association between the human myeloid immunoglobulin A Fc receptor (CD89) and FcRg chain. Molecular basis for CD89/FcRg chain association. J Biol Chem 1995; 270:29781-7.
154. Kim MK, Huang ZY, Hwang PH, Jones BA, Sato N, Hunter S, et al. Fcg receptor transmembrane domains: role in cell surface expression, g chain interaction and phagocytosis. Blood 2003; 101:4479-84.
155. Singleton TE, Platzer B, Dehlink E, Fiebiger E. The first transmembrane region of the b-chain stabilizes the tetrameric FceRI complex. Mol Immunol 2009; 46:2333-9.
156. Angelov GS, Guillaume P, Cebecauer M, Bosshard G, Dojcinovic D, Baumgaertner P, et al. Soluble MHC-peptide complexes containing long rigid linkers abolish CTL-mediated cytotoxicity. J Immunol 2006; 176:3356-65.
157. Rotzschke O, Falk K, Strominger JL. Superactivation of an immune response triggered by oligomerized T cell epitopes. Proc Natl Acad Sci USA 1997; 94:14642-7.
158. Tamir I, Schweitzer-Stenner R, Pecht I. Immobilization of the type I receptor for IgE initiates signal transduction in mast cells. Biochemistry 1996; 35:6872-83.
159. Yang H, Parkhouse RM. Differential activation requirements associated with stimulation of T cells via different epitopes of CD3. Immunology 1998; 93:26-32.
160. Niederberger N, Buehler LK, Ampudia J, Gascoigne NR. Thymocyte stimulation by anti-TCR-beta, but not by anti-TCR-alpha, leads to induction of developmental transcription program. J Leukoc Biol 2005; 77:830-41.
161. Carreno LJ, Gonzalez PA, Kalergis AM. Modulation of T cell function by TCR/pMHC binding kinetics. Immunobiology 2006; 211:47-64.
162. Holler PD, Lim AR, Cho BK, Rund LA, Kranz DM. CD8(-) T cell transfectants that express a high affinity T cell receptor exhibit enhanced peptide-dependent activation. J Exp Med 2001; 194:1043-52.
163. Ortega E, Schweitzer-Stenner R, Pecht I. Possible orientational constraints determine secretory signals induced by aggregation of IgE receptors on mast cells. EMBO J 1988; 7:4101-9.
164. Pecht I, Ortega E, Jovin TM. Rotational dynamics of the Fce receptor on mast cells monitored by specific monoclonal antibodies and IgE. Biochemistry 1991; 30:3450-8.
165. Gil D, Schamel WW, Montoya M, Sanchez-Madrid F, Alarcon B. Recruitment of Nck by CD3e reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell 2002; 109:901-12.
166. Tamir I, Cambier JC. Antigen receptor signaling: integration of protein tyrosine kinase functions. Oncogene 1998; 17:1353-64.
167. Sulzer B, Perelson AS. Immunons revisited: binding of multivalent antigens to B cells. Mol Immunol 1997; 34:63-74.
168. Reth M, Wienands J. Initiation and processing of signals from the B cell antigen receptor. Annu Rev Immunol 1997; 15:453-79.
169. Nimmerjahn F. Activating and inhibitory FcgRs in autoimmune disorders. Springer Semin Immunopathol 2006; 28:305-19.
170. Maurer D, Fiebiger E, Reininger B, Ebner C, Petzelbauer P, Shi GP, et al. Fce receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation. J Immunol 1998; 161:2731-9.
171. Lara M, Ortega E, Pecht I, Pfeiffer JR, Martinezm AM, Lee RJ, et al. Overcoming the signaling defect of Lyn-sequestering, signal-curtailing FceRI dimers: aggregated dimers can dissociate from Lyn and form signaling complexes with Syk. J Immunol 2001; 167:4329-37.
172. Metzger H. The high affinity receptor for IgE, FceRI. Novartis Found Symp 2004; 257:51-9.
173. Metzger H, Eglite S, Haleem-Smith H, Reischl I, Torigoe C. Quantitative aspects of signal transduction by the receptor with high affinity for IgE. Mol Immunol 2002; 38:1207-11.
174. Holowka D, Sil D, Torigoe C, Baird B. Insights into immunoglobulin E receptor signaling from structurally defined ligands. Immunol Rev 2007; 217:269- 79.
175. Radaev S, Sun PD. Structure and function of natural killer cell surface receptors. Annu Rev Biophys Biomol Struct 2003; 32:93-114.
176. Natarajan K, Dimasi N, Wang J, Mariuzza RA, Margulies DH. Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annu Rev Immunol 2002; 20:853-85.
177. Turnbull IR, Colonna M. Activating and inhibitory functions of DAP12. Nat Rev Immunol 2007; 7:155-61.
178. Posner RG, Paar JM, Licht A, Pecht I, Conrad DH, Hlavacek WS. Interaction of a monoclonal IgE-specific antibody with cell-surface IgE-FceRI: characterization of equilibrium binding and secretory response. Biochemistry 2004; 43:11352-60.
179. Schweitzer-Stenner R, Ortega E, Pecht I. Kinetics of FceRI dimer formation by specific monoclonal antibodies on mast cells. Biochemistry 1994; 33:8813- 25.
180. Kent UM, Mao SY, Wofsy C, Goldstein B, Ross S, Metzger H. Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE. Proc Natl Acad Sci USA 1994; 91:3087-91.
181. Yamasaki S, Ishikawa E, Kohno M, Saito T. The quantity and duration of FcRg signals determine mast cell degranulation and survival. Blood 2004; 103:3093-101.
182. Gibbs BF, Rathling A, Zillikens D, Huber M, Haas H. Initial FceRI-mediated signal strength plays a keyn role in regulating basophil signaling and deactivation. J Allergy Clin Immunol 2006; 118:1060-7.
183. Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffie C, et al. Identification of FcaRI as an inhibitory receptor that controls inflammation: dual role of FcRg ITAM. Immunity 2005; 22:31-42.
184. Varma R, Campi G, Yokosuka T, Saito T, Dustin ML. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Immunity 2006; 25:117-27.
185. Mescher MF, Agarwal P, Casey KA, Hammerbeck CD, Xiao Z, Curtsinger JM. Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus activation. Semin Immunol 2007; 19:153-61.
186. Colombetti S, Benigni F, Basso V, Mondino A. Clonal anergy is maintained independently of T cell proliferation. J Immunol 2002; 169:6178-86.
187. Choi S, Schwartz RH. Molecular mechanisms for adaptive tolerance and other T cell anergy models. Semin Immunol 2007; 19:140-52.
188. Chiodetti L, Choi S, Barber DL, Schwartz RH. Adaptive tolerance and clonal anergy are distinct biochemical states. J Immunol 2006; 176:2279-91.
189. Gu H. Anergic signals: the action is upstream. Immunity 2008; 28:598-600.
190. Teague RM, Greenberg PD, Fowler C, Huang MZ, Tan X, Morimoto J, et al. Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor. Immunity 2008; 28:662-74.
191. Srinivasan M, Frauwirth KA. Peripheral tolerance in CD8+ T cells. Cytokine 2009; 46:147-59.
192. Recio MJ, Moreno-Pelayo MA, Kilic SS, Guardo AC, Sanal O, Allende LM, et al. Differential biological role of CD3 chains revealed by human immunodeficiencies. J Immunol 2007; 178:2556-64.
193. Gil D, Schrum AG, Alarcon B, Palmer E. T cell receptor engagement by peptide-MHC ligands induces a conformational change in the CD3 complex of thymocytes. J Exp Med 2005; 201:517-22.
194. Risueno RM, Gil D, Fernandez E, Sanchez-Madrid F, Alarcon B. Ligand-induced conformational change in the T-cell receptor associated with productive immune synapses. Blood 2005; 106:601-8.
195. Risueno RM, van Santen HM, Alarcon B. A conformational change senses the strength of T cell receptor-ligand interaction during thymic selection. Proc Natl Acad Sci USA 2006; 103:9625-30.
196. Vilen BJ, Nakamura T, Cambier JC. Antigenstimulated dissociation of BCR mIg from Ig-a/Ig-b: implications for receptor desensitization. Immunity 1999; 10:239-48.
197. Vilen BJ, Famiglietti SJ, Carbone AM, Kay BK, Cambier JC. B cell antigen receptor desensitization: disruption of receptor coupling to tyrosine kinase activation. J Immunol 1997; 159:231-43.
198. Cambier JC, Fisher CL, Pickles H, Morrison DC. Dual molecular mechanisms mediate ligand-induced membrane Ig desensitization. J Immunol 1990; 145:13-9.
199. Vilen BJ, Burke KM, Sleater M, Cambier JC. Transmodulation of BCR signaling by transduction- incompetent antigen receptors: implications for impaired signaling in anergic B cells. J Immunol 2002; 168:4344-51.
200. Arnon TI, Achdout H, Levi O, Markel G, Saleh N, Katz G, et al. Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Nat Immunol 2005; 6:515-23.
201. Levit MN, Liu Y, Stock JB. Stimulus response coupling in bacterial chemotaxis: receptor dimers in ignalling arrays. Mol Microbiol 1998; 30:459-66.
202. Sourjik V, Berg HC. Functional interactions between receptors in bacterial chemotaxis. Nature 2004; 428:437-41.
203. Sourjik V. Receptor clustering and signal processing in E. coli chemotaxis. Trends Microbiol 2004; 12:569-76.
204. Kawaguchi M, Eckels DD. Differential activation through the TCR-CD3 complex affects the requirement for costimulation of human T cells. Hum Immunol 1995; 43:136-48.
205. Lanier LL, Ruitenberg JJ, Allison JP, Weiss A. Distinct epitopes on the T cell antigen receptor of HPB-ALL tumor cells identified by monoclonal antibodies. J Immunol 1986; 137:2286-92.
206. Schlitt HJ, Kurrle R, Wonigeit K. T cell activation by monoclonal antibodies directed to different epitopes on the human T cell receptor/CD3 complex: evidence for two different modes of activation. Eur J Immunol 1989; 19:1649-55.
207. Schwinzer R, Franklin RA, Domenico J, Renz H, Gelfand EW. Monoclonal antibodies directed to different epitopes in the CD3-TCR complex induce different states of competence in resting human T cells. J Immunol 1992; 148:1322-8.
208. Yoon ST, Dianzani U, Bottomly K, Janeway CA Jr. Both high and low avidity antibodies to the T cell receptor can have agonist or antagonist activity. Immunity 1994; 1:563-9.
209. Arkin M. Protein-protein interactions and cancer: small molecules going in for the kill. Curr Opin Chem Biol 2005; 9:317-24.
210. Ryan DP, Matthews JM. Protein-protein interactions in human disease. Curr Opin Struct Biol 2005; 15:441-6.
211. Veselovsky AV, Ivanov YD, Ivanov AS, Archakov AI, Lewi P, Janssen P. Protein-protein interactions: mechanisms and modification by drugs. J Mol Recognit 2002; 15:405-22.
212. Archakov AI, Govorun VM, Dubanov AV, Ivanov YD, Veselovsky AV, Lewi P, et al. Protein-protein interactions as a target for drugs in proteomics. Proteomics 2003; 3:380-91.
213. Pagliaro L, Felding J, Audouze K, Nielsen SJ, Terry RB, Krog-Jensen C, et al. Emerging classes of protein-protein interaction inhibitors and new tools for their development. Curr Opin Chem Biol 2004; 8:442-9.
214. Loregian A, Palu G. Disruption of protein-protein interactions: towards new targets for chemotherapy. J Cell Physiol 2005; 204:750-62.
215. Toogood PL. Inhibition of protein-protein association by small molecules: approaches and progress. J Med Chem 2002; 45:1543-58.
216. Fry DC. Protein-protein interactions as targets for small molecule drug discovery. Biopolymers 2006; 84:535-52.
217. Fletcher S, Hamilton AD. Targeting protein-protein interactions by rational design: mimicry of protein surfaces. J R Soc Interface 2006; 3:215-33.
218. Hershberger SJ, Lee SG, Chmielewski J. Scaffolds for blocking protein-protein interactions. Curr Top Med Chem 2007; 7:928-42.
219. Che Y, Brooks BR, Marshall GR. Development of small molecules designed to modulate proteinprotein interactions. J Comput Aided Mol Des 2006; 20:109-30.
220. Sillerud LO, Larson RS. Design and structure of peptide and peptidomimetic antagonists of proteinprotein interaction. Curr Protein Pept Sci 2005; 6:151-69.
221. Sigalov AB. Interaction between HIV gp41 fusion peptide and T cell receptor: putting the puzzle pieces back together. Faseb J 2007; 21:1633-4.
222. Sigalov AB. New therapeutic strategies targeting transmembrane signal transduction in the immune system. Cell Adh Migr 2010; 4.
223. Sigalov AB. More on: glycoprotein VI oligomerization: a novel concept of platelet inhibition. J Thromb Haemost 2007; 5:2310-2.
224. Reich Z, Boniface JJ, Lyons DS, Borochov N, Wachtel EJ, Davis MM. Ligand-specific oligomerization of T-cell receptor molecules. Nature 1997; 387:617-20.
225. Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 1996; 384:134-41.
226. Abastado JP, Lone YC, Casrouge A, Boulot G, Kourilsky P. Dimerization of soluble major histocompatibility complex-peptide complexes is sufficient for activation of T cell hybridoma and induction of unresponsiveness. J Exp Med 1995; 182:439-47.
227. Lindstedt R, Monk N, Lombardi G, Lechler R. Amino acid substitutions in the putative MHC class II "dimer of dimers" interface inhibit CD4+ T cell activation. J Immunol 2001; 166:800-8.
228. Hayball JD, Lake RA. The immune function of MHC class II molecules mutated in the putative superdimer interface. Mol Cell Biochem 2005; 273:1-9.
229. Watts TH. T cell activation by preformed, longlived Ia-peptide complexes. Quantitative aspects. J Immunol 1988; 141:3708-14.
230. Rubin B, Knibiehler M, Gairin JE. Allosteric Changes in the TCR/CD3 Structure Upon Interaction With Extra- or Intra-cellular Ligands. Scand J Immunol 2007; 66:228-37.
231. Minguet S, Schamel WW. Permissive geometry model. Adv Exp Med Biol 2008; 640:113-20.
232. Schamel WW, Reth M. Clustering models. Adv Exp Med Biol 2008; 640:64-73.
233. Cochran JR, Cameron TO, Stone JD, Lubetsky JB, Stern LJ. Receptor proximity, not intermolecular orientation, is critical for triggering T-cell activation. J Biol Chem 2001; 276:28068-74.
234. Cebecauer M, Guillaume P, Hozak P, Mark S, Everett H, Schneider P, et al. Soluble MHC-peptide complexes induce rapid death of CD8+ CTL. J Immunol 2005; 174:6809-19.
235. Yamasaki S, Ishikawa E, Sakuma M, Ogata K, Sakata-Sogawa K, Hiroshima M, et al. Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nat Immunol 2006; 7:67-75.
236. Yamasaki S, Saito T. Molecular basis for pre-TCRmediated autonomous signaling. Trends Immunol 2007; 28:39-43.
237. Geisberger R, Crameri R, Achatz G. Models of signal transduction through the B-cell antigen receptor. Immunology 2003; 110:401-10.
238. Yamashita T, Mao SY, Metzger H. Aggregation of the high-affinity IgE receptor and enhanced activity of p53/56lyn protein-tyrosine kinase. Proc Natl Acad Sci USA 1994; 91:11251-5.
239. Kane P, Erickson J, Fewtrell C, Baird B, Holowka D. Cross-linking of IgE-receptor complexes at the cell surface: synthesis and characterization of a long bivalent hapten that is capable of triggering mast cells and rat basophilic leukemia cells. Mol Immunol 1986; 23:783-90.
240. Kanamaru Y, Blank U, Monteiro RC. IgA Fc receptorI Is a molecular switch that determines IgA activating or inhibitory functions. Contrib Nephrol 2007; 157:148-52.
241. Powell MS, Hogarth PM. Fc receptors. Adv Exp Med Biol 2008; 640:22-34.
242. Li P, Morris DL, Willcox BE, Steinle A, Spies T, Strong RK. Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat Immunol 2001; 2:443-51.
243. Strong RK. Asymmetric ligand recognition by the activating natural killer cell receptor NKG2D, a symmetric homodimer. Mol Immunol 2002; 38:1029-37.
244. Farndale RW. Collagen-induced platelet activation. Blood Cells Mol Dis 2006; 36:162-5.
245. Smethurst PA, Onley DJ, Jarvis GE, O'Connor MN, Knight CG, Herr AB, et al. Structural basis for the platelet-collagen interaction: the smallest motif within collagen that recognizes and activates platelet Glycoprotein VI contains two glycine-proline-hydroxyproline triplets. J Biol Chem 2007; 282:1296-304.
246. Lu Q, Navdaev A, Clemetson JM, Clemetson KJ. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon 2005; 45:1089-98.
247. Kato K, Furihata K, Cheli Y, Radis-Baptista G, Kunicki TJ. Effect of multimer size and a natural dimorphism on the binding of convulxin to platelet glycoprotein (GP)VI. J Thromb Haemost 2006; 4:1107-13.
248. Horii K, Brooks MT, Herr AB. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: implications for platelet activation. Biochemistry 2009; 48:2907-14.
249. Singer KL, Mostov KE. Dimerization of the polymeric immunoglobulin receptor controls its transcytotic trafficking. Mol Biol Cell 1998; 9:901-15.
250. Mocsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol 2006; 7:1326-33.
251. Li R, Mitra N, Gratkowski H, Vilaire G, Litvinov R, Nagasami C, et al. Activation of integrin aIIbb3 by modulation of transmembrane helix associations. Science 2003; 300:795-8.
252. Hantgan RR, Lyles DS, Mallett TC, Rocco M, Nagaswami C, Weisel JW. Ligand binding promotes the entropy-driven oligomerization of integrin aIIbb3. J Biol Chem 2003; 278:3417-26.
253. Iber D, Gruhn T. Organisation of B-cell receptors on the cell membrane. Syst Biol (Stevenage) 2006; 153:401-4.
254. Matsuuchi L, Gold MR. New views of BCR structure and organization. Curr Opin Immunol 2001; 13:270-7.
255. Schamel WW, Reth M. Monomeric and oligomeric complexes of the B cell antigen receptor. Immunity 2000; 13:5-14.
256. Kim ST, Takeuchi K, Sun ZY, Touma M, Castro CE, Fahmy A, et al. The ab T cell receptor is an anisotropic mechanosensor. J Biol Chem 2009; 284:31028-37.
257. Moss WC, Irvine DJ, Davis MM, Krummel MF. Quantifying signaling-induced reorientation of T cell receptors during immunological synapse formation. Proc Natl Acad Sci USA 2002; 99:15024-1529.
258. Minguet S, Swamy M, Alarcon B, Luescher IF, Schamel WW. Full activation of the T cell receptor requires both clustering and conformational changes at CD3. Immunity 2007; 26:43-54.
259. Kato Z, Stern JN, Nakamura HK, Kuwata K, Kondo N, Strominger JL. Positioning of autoimmune TCR-Ob.2F3 and TCR-Ob.3D1 on the MBP85-99/HLA-DR2 complex. Proc Natl Acad Sci USA 2008; 105:15523-8.
260. Ding YH, Baker BM, Garboczi DN, Biddison WE, Wiley DC. Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity 1999; 11:45-56.
261. Ortega E, Lara M, Lee I, Santana C, Martinez AM, Pfeiffer JR, et al. Lyn dissociation from phosphorylated FceRI subunits: a new regulatory step in the FceRI signaling cascade revealed by studies of FceRI dimer signaling activity. J Immunol 1999; 162:176-85.
262. Siegers GM, Yang J, Duerr CU, Nielsen PJ, Reth M, Schamel WW. Identification of disulfide bonds in the Ig-a/Ig-b component of the B cell antigen receptor using the Drosophila S2 cell reconstitution system. Int Immunol 2006; 18:1385-96.
263. Su Z, Wang H, Wan Y, Bi Z. In vitro preparation and characterization of the human CD3ee homodimer and CD3eg and CD3ed heterodimers. Int J Mol Med 2009; 24:437-44.
264. Asai K, Fujimoto K, Harazaki M, Kusunoki T, Korematsu S, Ide C, et al. Distinct aggregation of b- and g-chains of the high-affinity IgE receptor on cross-linking. J Histochem Cytochem 2000; 48:1705-16.
265. Kishimoto H, Kubo RT, Yorifuji H, Nakayama T, Asano Y, Tada T. Physical dissociation of the TCRCD3 complex accompanies receptor ligation. J Exp Med 1995; 182:1997-2006.
266. Kosugi A, Saitoh S, Noda S, Yasuda K, Hayashi F, Ogata M, et al. Translocation of tyrosine-phosphorylated TCRzeta chain to glycolipid-enriched membrane domains upon T cell activation. Int Immunol 1999; 11:1395-401.
267. La Gruta NL, Liu H, Dilioglou S, Rhodes M, Wiest DL, Vignali DA. Architectural changes in the TCR:CD3 complex induced by MHC:Peptide ligation. J Immunol 2004; 172:3662-9
268. Liu H, Rhodes M, Wiest DL, Vignali DA. On the dynamics of TCR:CD3 complex cell surface expression and downmodulation. Immunity 2000; 13:665-75.
269. D'Oro U, Munitic I, Chacko G, Karpova T, McNally J, Ashwell JD. Regulation of constitutive TCR internalization by the z-chain. J Immunol 2002; 169:6269-78.
270. Ouchida R, Yamasaki S, Hikida M, Masuda K, Kawamura K, Wada A, et al. A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3z-chain degradation. Immunity 2008; 29:33-43.
271. McKay DB, Irie HY, Hollander G, Ferrara JL, Strom TB, Li Y, et al. Antigen-induced unresponsiveness results in altered T cell signaling. J Immunol 1999; 163:6455-61.
272. Willems F, Andris F, Xu D, Abramowicz D, Wissing M, Goldman M, et al. The induction of human T cell unresponsiveness by soluble anti-CD3 mAb requires T cell activation. Int Immunol 1995; 7:1593-8.
273. Wang XM, Djordjevic JT, Kurosaka N, Schibeci S, Lee L, Williamson P, et al. T-cell antigen receptor peptides inhibit signal transduction within the membrane bilayer. Clin Immunol 2002; 105:199-207.
274. Kim JH, Cramer L, Mueller H, Wilson B, Vilen BJ. Independent trafficking of Ig-a/Ig-b and mu-heavy chain is facilitated by dissociation of the B cell antigen receptor complex. J Immunol 2005; 175:147-54.
275. Kremyanskaya M, Monroe JG. Ig-independent Igb expression on the surface of B lymphocytes after B cell receptor aggregation. J Immunol 2005; 174:1501-6.
276. Gascoigne NR, Zal T, Alam SM. T-cell receptor binding kinetics in T-cell development and activation. Expert Rev Mol Med 2001; 2001:1-17.
277. Germain RN, Stefanova I. The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annu Rev Immunol 1999; 17:467-522.
278. Engelhardt JJ, Krummel MF. The importance of prolonged binding to antigen-presenting cells for T cell fate decisions. Immunity 2008; 28:143-5.
279. Scholer A, Hugues S, Boissonnas A, Fetler L, Amigorena S. Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity 2008; 28:258-70.
280. Rosette C, Werlen G, Daniels MA, Holman PO, Alam SM, Travers PJ, et al. The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model. Immunity 2001; 15:59-70.
281. Goldstein B, Coombs D, Faeder JR, Hlavacek WS. Kinetic proofreading model. Adv Exp Med Biol 2008; 640:82-94.
282. Werlen G, Hausmann B, Naeher D, Palmer E. Signaling life and death in the thymus: timing is everything. Science 2003; 299:1859-63.
283. Love PE, Lee J, Shores EW. Critical relationship between TCR signaling potential and TCR affinity during thymocyte selection. J Immunol 2000; 165:3080-7.
284. Mirshahidi S, Ferris LC, Sadegh-Nasseri S. The magnitude of TCR engagement is a critical predictor of T cell anergy or activation. J Immunol 2004; 172:5346-55.
285. Gett AV, Sallusto F, Lanzavecchia A, Geginat J. T cell fitness determined by signal strength. Nat Immunol 2003; 4:355-60.
286. Langenkamp A, Casorati G, Garavaglia C, Dellabona P, Lanzavecchia A, Sallusto F. T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification. Eur J Immunol 2002; 32:2046-54.
287. Varma R. TCR triggering by the pMHC complex: valency, affinity and dynamics. Sci Signal 2008; 1:21.
288. Naeher D, Daniels MA, Hausmann B, Guillaume P, Luescher I, Palmer E. A constant affinity threshold for T cell tolerance. J Exp Med 2007; 204:2553-9.
289. Batista FD, Neuberger MS. Affinity dependence of the B cell response to antigen: a threshold, a ceiling, and the importance of off-rate. Immunity 1998; 8:751-9.
290. Casola S, Otipoby KL, Alimzhanov M, Humme S, Uyttersprot N, Kutok JL, et al. B cell receptor signal strength determines B cell fate. Nat Immunol 2004; 5:317-27.
291. Benschop RJ, Cambier JC. B cell development: signal transduction by antigen receptors and their surrogates. Curr Opin Immunol 1999; 11:143-51.
292. George J, Penner SJ, Weber J, Berry J, Claflin JL. Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation. J Immunol 1993; 151:5955-65.
293. Singh DK, Kumar D, Siddiqui Z, Basu SK, Kumar V, Rao KV. The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal. Cell 2005; 121:281-93.
294. Kinet JP. The high-affinity IgE receptor (FceRI): from physiology to pathology. Annu Rev Immunol 1999; 17:931-72.
295. Yamasaki S, Saito T. Regulation of mast cell activation through FceRI. Chem Immunol Allergy 2005; 87:22-31.
296. Hlavacek WS, Redondo A, Wofsy C, Goldstein B. Kinetic proofreading in receptor-mediated transduction of cellular signals: receptor aggregation, partially activated receptor, and cytosolic messengers. Bull Math Biol 2002; 64:887-911.
297. Iwashima M. Kinetic perspectives of T cell antigen receptor signaling. A two-tier model for T cell full activation. Immunol Rev 2003; 191:196-210.
298. Hlavacek WS, Redondo A, Metzger H, Wofsy C, Goldstein B. Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading. Proc Natl Acad Sci USA 2001; 98:7295-300.
299. Ono S, Ohno H, Saito T. Rapid turnover of the CD3z chain independent of the TCR-CD3 complex in normal T cells. Immunity 1995; 2:639-44.
300. Holst J, Wang H, Eder KD, Workman CJ, Boyd KL, Baquet Z, et al. Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nat Immunol 2008; 9:658-66.
301. Malissen B. CD3 ITAMs count! Nat Immunol 2008; 9:583-4.
302. McKeithan TW. Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 1995; 92:5042-6.
303. Rabinowitz JD, Beeson C, Lyons DS, Davis MM, McConnell HM. Kinetic discrimination in T-cell activation. Proc Natl Acad Sci USA 1996; 93:1401-5.
304. Rabinowitz JD, Beeson C, Wulfing C, Tate K, Allen PM, Davis MM, et al. Altered T cell receptor ligands trigger a subset of early T cell signals. Immunity 1996; 5:125-35.
305. Kersh GJ, Kersh EN, Fremont DH, Allen PM. Highand low-potency ligands with similar affinities for the TCR: the importance of kinetics in TCR signaling. Immunity 1998; 9:817-26.
306. Schamel WW, Risueno RM, Minguet S, Ortiz AR, Alarcon B. A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex. Trends Immunol 2006; 27:176-82.
307. Valitutti S, Muller S, Cella M, Padovan E, Lanzavecchia A. Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature 1995; 375:148-51.
308. Itoh Y, Hemmer B, Martin R, Germain RN. Serial TCR engagement and down-modulation by peptide:MHC molecule ligands: relationship to the quality of individual TCR signaling events. J Immunol 1999; 162:2073-80.
309. Borovsky Z, Mishan-Eisenberg G, Yaniv E, Rachmilewitz J. Serial triggering of T cell receptors results in incremental accumulation of signaling intermediates. J Biol Chem 2002; 277:21529-36.
310. Sousa J, Carneiro J. A mathematical analysis of TCR serial triggering and downregulation. Eur J Immunol 2000; 30:3219-27.
311. Friedl P, Gunzer M. Interaction of T cells with APCs: the serial encounter model. Trends Immunol 2001; 22:187-91.
312. Davis MM. A new trigger for T cells. Cell 2002; 110:285-7.
313. Alarcon B, Gil D, Delgado P, Schamel WW. Initiation of TCR signaling: regulation within CD3 dimers. Immunol Rev 2003; 191:38-46.
314. Reth M, Wienands J, Schamel WW. An unsolved problem of the clonal selection theory and the model of an oligomeric B-cell antigen receptor. Immunol Rev 2000; 176:10-8.
315. Aivazian D, Stern LJ. Phosphorylation of T cell receptor z is regulated by a lipid dependent folding transition. Nat Struct Biol 2000; 7:1023-6.
316. Rojo JM, Janeway CA Jr. The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized. J Immunol 1988; 140:1081-8.
317. Krogsgaard M, Prado N, Adams EJ, He XL, Chow DC, Wilson DB, et al. Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T cell activation. Mol Cell 2003; 12:1367-78.
318. Kjer-Nielsen L, Dunstone MA, Kostenko L, Ely LK, Beddoe T, Mifsud NA, et al. Crystal structure of the human T cell receptor CD3eg heterodimer complexed to the therapeutic mAb OKT3. Proc Natl Acad Sci USA 2004; 101:7675-80.
319. Levin SE, Weiss A. Twisting tails exposed: the evidence for TCR conformational change. J Exp Med 2005; 201:489-92.
320. Anton van der Merwe P, Davis SJ, Shaw AS, Dustin ML. Cytoskeletal polarization and redistribution of cell-surface molecules during T cell antigen recognition. Semin Immunol 2000; 12:5-21
321. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998; 395:82-6.
322. Davis SJ, van der Merwe PA. The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 2006; 7:803-9.
323. Kuhns MS, Davis MM. The safety on the TCR trigger. Cell 2008; 135:594-6.
324. Xu C, Gagnon E, Call ME, Schnell JR, Schwieters CD, Carman CV, et al. Regulation of T cell receptor activation by dynamic membrane binding of the CD3e cytoplasmic tyrosine-based motif. Cell 2008; 135:702-13.
325. Manolios N, Ali M, Amon M, Bender V. Therapeutic application of transmembrane T and natural killer cell receptor peptides. Adv Exp Med Biol 2008; 640:208-19.
326. Manolios N, Collier S, Taylor J, Pollard J, Harrison LC, Bender V. T-cell antigen receptor transmembrane peptides modulate T-cell function and T cellmediated disease. Nat Med 1997; 3:84-8.
327. Ali M, De Planque MRR, Huynh NT, Manolios N, Separovic F. Biophysical studies of a transmembrane peptide derived from the T cell antigen receptor. Lett Pept Sci 2002; 8:227-33.
328. Bender V, Ali M, Amon M, Diefenbach E, Manolios N. T cell antigen receptor peptide-lipid membrane interactions using surface plasmon resonance. J Biol Chem 2004; 279:54002-7.
329. Gerber D, Quintana FJ, Bloch I, Cohen IR, Shai Y. D-enantiomer peptide of the TCRa transmembrane domain inhibits T-cell activation in vitro and in vivo. Faseb J 2005; 19:1190-2.
330. Enk AH, Knop J. T cell receptor mimic peptides and their potential application in T-cell-mediated disease. Int Arch Allergy Immunol 2000; 123:275-81.
331. Gollner GP, Muller G, Alt R, Knop J, Enk AH. Therapeutic application of T cell receptor mimic peptides or cDNA in the treatment of T cell-mediated skin diseases. Gene Ther 2000; 7:1000-4.
332. Manolios N, Huynh NT, Collier S. Peptides in the treatment of inflammatory skin disease. Australas J Dermatol 2002; 43:226-7.
333. Kurosaka N, Bolte A, Ali M, Manolios N. T-cell antigen receptor assembly and cell surface expression is not affected by treatment with T-cell antigen receptor-a chain transmembrane Peptide. Protein Pept Lett 2007; 14:299-303.
334. Collier S, Bolte A, Manolios N. Discrepancy in CD3-transmembrane peptide activity between in vitro and in vivo T-cell inhibition. Scand J Immunol 2006; 64:388-91.
335. Amon MA, Ali M, Bender V, Chan YN, Toth I, Manolios N. Lipidation and glycosylation of a T cell antigen receptor (TCR) transmembrane hydrophobic peptide dramatically enhances in vitro and in vivo function. Biochim Biophys Acta 2006.
336. Ali M, Salam NK, Amon M, Bender V, Hibbs DE, Manolios N. T-Cell Antigen Receptor-alpha Chain Transmembrane Peptides: Correlation between Structure and Function. Int J Pept Res Ther 2006; 12:261-7.
337. Vandebona H, Ali M, Amon M, Bender V, Manolios N. Immunoreceptor transmembrane peptides and their effect on natural killer (NK) cell cytotoxicity. Protein Pept Lett 2006; 13:1017-24
338. Sigalov AB. Novel mechanistic concept of platelet inhibition. Expert Opin Ther Targets 2008; 12:677-92.
339. Sigalov AB. Novel mechanistic insights into viral modulation of immune receptor signaling. PLoS Pathog 2009; 5:1000404.
340. Kim WM, Sigalov AB. Viral pathogenesis, modulation of immune receptor signaling and treatment. Adv Exp Med Biol 2008; 640:325-49.
341. Spencer DM, Wandless TJ, Schreiber SL, Crabtree GR. Controlling signal transduction with synthetic ligands. Science 1993; 262:1019-24.
342. Soldevila G, Castellanos C, Malissen M, Berg LJ. Analysis of the individual role of the TCRz chain in transgenic mice after conditional activation with chemical inducers of dimerization. Cell Immunol 2001; 214:123-38.
343. Crabtree GR, Schreiber SL. Three-part inventions: intracellular signaling and induced proximity. Trends Biochem Sci 1996; 21:418-22.
344. Buferne M, Luton F, Letourneur F, Hoeveler A, Couez D, Barad M, et al. Role of CD3d in surface expression of the TCR/CD3 complex and in activation for killing analyzed with a CD3d-negative cytotoxic T lymphocyte variant. J Immunol 1992; 148:657-64.
345. Luton F, Buferne M, Legendre V, Chauvet E, Boyer C, Schmitt-Verhulst AM. Role of CD3g and CD3d cytoplasmic domains in cytolytic T lymphocyte functions and TCR/CD3 downmodulation. J Immunol 1997; 158:4162-70.
346. Haks MC, Cordaro TA, van den Brakel JH, Haanen JB, de Vries EF, Borst J, et al. A redundant role of the CD3g-immunoreceptor tyrosine-based activation motif in mature T cell function. J Immunol 2001; 166:2576-88.
347. Haks MC, Pepin E, van den Brakel JH, Smeele SA, Belkowski SM, Kessels HW, et al. Contributions of the T cell receptor-associated CD3g-ITAM to thymocyte selection. J Exp Med 2002; 196:1-13
348. de Saint Basile G, Geissmann F, Flori E, Uring-Lambert B, Soudais C, Cavazzana-Calvo M, et al. Severe combined immunodeficiency caused by deficiency in either the d or the e subunit of CD3. J Clin Invest 2004; 114:1512-7.
349. Roifman CM. CD3d immunodeficiency. Curr Opin Allergy Clin Immunol 2004; 4:479-84.
350. Teixeiro E, Daniels MA, Hausmann B, Schrum AG Naeher D, Luescher I, et al. T cell division and death are segregated by mutation of TCRb chain constant domains. Immunity 2004; 21:515-26
351. Teixeiro E, Daniels MA, Hamilton SE, Schrum AG, Bragado R, Jameson SC, et al. Different T cell receptor signals determine CD8+ memory versus effector development. Science 2009; 323:502-5
352. Torres PS, Zapata DA, Pacheco-Castro A, Rodriguez-Fernandez JL, Cabanas C, Regueiro JR. Contribution of CD3g to TCR regulation and signaling in human mature T lymphocytes. Int Immunol 2002; 14:1357-67.
353. Rodriguez-Tarduchy G, Sahuquillo AG, Alarcon B, Bragado R. Apoptosis but not other activation events is inhibited by a mutation in the transmembrane domain of T cell receptor b that impairs CD3z association. J Biol Chem 1996; 271:30417-25.
354. Sutton BJ, Gould HJ. The human IgE network. Nature 1993; 366:421-8.
355. Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, et al. The biology of IGE and the basis of allergic disease. Annu Rev Immunol 2003; 21:579-628.
356. Kraft S, Novak N. Fc receptors as determinants of allergic reactions. Trends Immunol 2006; 27:88-95
357. Adamczewski M, Paolini R, Kinet JP. Evidence for two distinct phosphorylation pathways activated by high affinity immunoglobulin E receptors. J Biol Chem 1992; 267:18126-32.
358. Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH, Kinet JP. Allergy-associated FcRb is a molecular amplifier of IgE- and IgG-mediated in vivo responses. Immunity 1998; 8:517-29
359. Eiseman E, Bolen JB. Signal transduction by the cytoplasmic domains of FceRI-g and TCR-z in rat basophilic leukemia cells. J Biol Chem 1992; 267:21027-32.
360. Jouvin MH, Adamczewski M, Numerof R, Letourneur O, Valle A, Kinet JP. Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. J Biol Chem 1994; 269:5918-25.
361. Scharenberg AM, Lin S, Cuenod B, Yamamura H, Kinet JP. Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering. EMBO J 1995; 14:3385-94.
362. Shiue L, Green J, Green OM, Karas JL, Morgenstern JP, Ram MK, et al. Interaction of p72syk with the g and b subunits of the high-affinity receptor for immunoglobulin E, FceRI. Mol Cell Biol 1995; 15:272-81.
363. Wilson BS, Kapp N, Lee RJ, Pfeiffer JR, Martinez AM, Platt Y, et al. Distinct functions of the FceR1g and b subunits in the control of FceR1-mediated tyrosine kinase activation and signaling responses in RBL-2H3 mast cells. J Biol Chem 1995; 270:4013-22.
364. Goldstein B, Faeder JR, Hlavacek WS. Mathematical and computational models of immune-receptor signalling. Nat Rev Immunol 2004; 4:445-56.
365. Goldstein B, Faeder JR, Hlavacek WS, Blinov ML, Redondo A, Wofsy C. Modeling the early signaling events mediated by FceR1. Mol Immunol 2002; 38:1213-9.
366. Faeder JR, Hlavacek WS, Reischl I, Blinov ML, Metzger H, Redondo A, et al. Investigation of early events in FceR1-mediated signaling using a detailed mathematical model. J Immunol 2003; 170:3769-81.
367. Hlavacek WS, Faeder JR, Blinov ML, Perelson AS, Goldstein B. The complexity of complexes in signal transduction. Biotechnol Bioeng 2003; 84:783-94.
368. Nadler MJ, Matthews SA, Turner H, Kinet JP. Signal transduction by the high-affinity immunoglobulin E receptor FceR1: coupling form to function. Adv Immunol 2000; 76:325-55.
369. Liu KJ, Parikh VS, Tucker PW, Kim BS. Role of the B cell antigen receptor in antigen processing and presentation. Involvement of the transmembrane region in intracellular trafficking of receptor/ligand complexes. J Immunol 1993; 151:6143-54.
370. Pleiman CM, D'Ambrosio D, Cambier JC. The B-cell antigen receptor complex: structure and signal transduction. Immunol Today 1994; 15:393-9.
371. Cambier JC. Signal transduction by T- and B-cell antigen receptors: converging structures and concepts. Curr Opin Immunol 1992; 4:257-64.
372. Cambier JC, Pleiman CM, Clark MR. Signal transduction by the B cell antigen receptor and its coreceptors. Annu Rev Immunol 1994; 12:457-86.
373. Kraus M, Pao LI, Reichlin A, Hu Y, Canono B, Cambier JC, et al. Interference with immunoglobulin (Ig)a immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igb cytoplasmic tail. J Exp Med 2001; 194:455-69.
374. Batista FD, Iber D, Neuberger MS. B cells acquire antigen from target cells after synapse formation. Nature 2001; 411:489-94.
375. Bannish G, Fuentes-Panana EM, Cambier JC, Pear WS, Monroe JG. Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis. J Exp Med 2001; 194:1583-96.
376. Kato K, Kanaji T, Russell S, Kunicki TJ, Furihata K, Kanaji S, et al. The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletion. Blood 2003; 102:1701-7.
377. Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium. Cardiovasc Res 2004; 61:498-511.
378. Gibbins JM, Okuma M, Farndale R, Barnes M, Watson SP. Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor g-chain. FEBS Lett 1997; 413:255-9.
379. Sigalov AB. Inhibiting Collagen-induced Platelet Aggregation and Activation with Peptide Variants. US 12/001,258 and PCT PCT/US2007/025389 patent applications filed on 12/11/2007 and 12/12/2007, respectively, claiming a priority to US 60/874,694 provisional patent application filed on 12/13/2006.
380. Leitenberg D, Balamuth F, Bottomly K. Changes in the T cell receptor macromolecular signaling complex and membrane microdomains during T cell development and activation. Semin Immunol 2001; 13:129-38.
381. Janeway CA Jr, Bottomly K. Responses of T cells to ligands for the T-cell receptor. Semin Immunol 1996; 8:108-15.
382. Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell 1994; 76:275-85
383. Niedergang F, Dautry-Varsat A, Alcover A. Peptide antigen or superantigen-induced downregulation of TCRs involves both stimulated and unstimulated receptors. J Immunol 1997; 159:1703-10
384. Bonefeld CM, Rasmussen AB, Lauritsen JP, von Essen M, Odum N, Andersen PS, et al. TCR comodulation of nonengaged TCR takes place by a protein kinase C and CD3g di-leucine-based motif-dependent mechanism. J Immunol 2003; 171:3003-9.
385. San Jose E, Borroto A, Niedergang F, Alcover A, Alarcon B. Triggering the TCR complex causes the downregulation of nonengaged receptors by a signal transduction-dependent mechanism. Immunity 2000; 12:161-70.
386. von Essen M, Nielsen MW, Bonefeld CM, Boding L, Larsen JM, Leitges M, et al. Protein kinase C (PKC)a and PKCt are the major PKC isotypes involved in TCR downregulation. J Immunol 2006; 176:7502-10
387. Quintana FJ, Gerber D, Kent SC, Cohen IR, Shai Y. HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation. J Clin Invest 2005; 115:2149-58.
388. Bloch I, Quintana FJ, Gerber D, Cohen T, Cohen IR, Shai Y. T-Cell inactivation and immunosuppressive activity induced by HIV gp41 via novel interacting motif. Faseb J 2007; 21:393-401.
389. Alarcon B, Swamy M, van Santen HM, Schamel WW. T-cell antigen-receptor stoichiometry: preclustering for sensitivity. EMBO Rep 2006; 7:490-5
390. Kim YM, Pan JY, Korbel GA, Peperzak V, Boes M, Ploegh HL. Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation. Proc Natl Acad Sci USA 2006; 103:3327-32.
391. Eynon EE, Parker DC. Small B cells as antigenpresenting cells in the induction of tolerance to soluble protein antigens. J Exp Med 1992; 175:131-8.
392. Gahring LC, Weigle WO. The induction of peripheral T cell unresponsiveness in adult mice by monomeric human g-globulin. J Immunol 1989; 143:2094-100.