Mechanical regulation of T-cell functions

Immunological Reviews

Volumn 256, Issue 1, 2013, Pages 160-176

  Chen, Wei ^a   Zhu, Cheng ^a,b  

^a GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^b GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Catch bonds; Cell surface receptors; Conformational change; Mechanoregulated molecular interaction; Mechanosensing; Protein mechanochemistry

Indexed keywords

ACTIN; ALPHA4 INTEGRIN; APC PROTEIN; CD3 ANTIGEN; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; L SELECTIN; MUCIN; P SELECTIN GLYCOPROTEIN LIGAND 1; PADGEM PROTEIN; PROTEIN KINASE ZAP 70; PROTEIN TYROSINE KINASE; T LYMPHOCYTE RECEPTOR;

ACTIN FILAMENT; ARTICLE; CELL ADHESION; CONFORMATIONAL TRANSITION; DECELERATION; FORCE; HUMAN; IMMUNOLOGICAL SYNAPSE; INFLAMMATION; LYMPHOCYTE MIGRATION; MICROENVIRONMENT; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; T LYMPHOCYTE;

CATCH BONDS; CELL SURFACE RECEPTORS; CONFORMATIONAL CHANGE; MECHANOREGULATED MOLECULAR INTERACTION; MECHANOSENSING; PROTEIN MECHANOCHEMISTRY;

ANIMALS; CELL MOVEMENT; HUMANS; IMMUNOLOGICAL SYNAPSES; INTEGRINS; LYMPHOCYTE ACTIVATION; PROTEIN CONFORMATION; RECEPTORS, IMMUNOLOGIC; T-LYMPHOCYTES;

EID: 84885347038     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12122     Document Type: Article

References (161)

1. Petrie HT, Zúñiga-Pflücker JC. Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol 2007;25:649-679.
2. Koch U, Radtke F. Mechanisms of T cell development and transformation. Annu Rev Cell Dev Biol 2011;27:539-562.
3. Love PE, Bhandoola A. Signal integration and crosstalk during thymocyte migration and emigration. Nat Rev Immunol 2011;11:469-477.
4. von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med 2000;343:1020-1034.
5. Huppa JB, Davis MM. T-cell-antigen recognition and the immunological synapse. Nat Rev Immunol 2003;3:973-983.
6. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 2007;7:678-689.
7. Dustin ML. Modular design of immunological synapses and kinapses. Cold Spring Harb Perspect Biol 2009;1:a002873.
8. Judokusumo E, Tabdanov E, Kumari S, Dustin ML, Kam LC. Mechanosensing in T lymphocyte activation. Biophys J 2012;102:L5-7.
9. O'Connor RS, et al. Substrate rigidity regulates human T cell activation and proliferation. J Immunol 2012;189:1330-1339.
10. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 2006;126:677-689.
11. Fu J, et al. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods 2010;7:733-736.
12. Saha K, et al. Substrate modulus directs neural stem cell behavior. Biophys J 2008;95:4426-4438.
13. Shin J-W, Swift J, Ivanovska I, Spinler KR, Buxboim A, Discher DE. Mechanobiology of bone marrow stem cells: from myosin-II forces to compliance of matrix and nucleus in cell forms and fates. Differentiation 2013; doi:10.1016/j.diff.2013.05.001.
14. Luster AD, Alon R, Andrian, von, UH. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 2005;6:1182-1190.
15. McEver RP, Zhu C. Rolling cell adhesion. Annu Rev Cell Dev Biol 2010;26:363-396.
16. Yago T, Zarnitsyna VI, Klopocki AG, McEver RP, Zhu C. Transport governs flow-enhanced cell tethering through L-selectin at threshold shear. Biophys J 2007;92:330-342.
17. Marshall BT, Long M, Piper JW, Yago T, McEver RP, Zhu C. Direct observation of catch bonds involving cell-adhesion molecules. Nature 2003;423:190-193.
18. Sarangapani KK, et al. Low force decelerates L-selectin dissociation from P-selectin glycoprotein ligand-1 and endoglycan. J Biol Chem 2004;279:2291-2298.
19. Wayman AM, Chen W, McEver RP, Zhu C. Triphasic force dependence of E-selectin/ligand dissociation governs cell rolling under flow. Biophys J 2010;99:1166-1174.
20. Zhu C, Yago T, Lou J, Zarnitsyna VI, McEver RP. Mechanisms for flow-enhanced cell adhesion. Ann Biomed Eng 2008;36:604-621.
21. Miner JJ, et al. Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow. Blood 2008;112:2035-2045.
22. Zarbock A, Abram CL, Hundt M, Altman A, Lowell CA, Ley K. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med 2008;205:2339-2347.
23. Kuwano Y, Spelten O, Zhang H, Ley K, Zarbock A. Rolling on E- or P-selectin induces the extended but not high-affinity conformation of LFA-1 in neutrophils. Blood 2010;116:617-624.
24. Shao B, et al. Signal-dependent slow leukocyte rolling does not require cytoskeletal anchorage of P-selectin glycoprotein ligand-1 (PSGL-1) or integrin αLβ2. J Biol Chem 2012;287:19585-19598.
25. Lefort CT, et al. Distinct roles for talin-1 and kindlin-3 in LFA-1 extension and affinity regulation. Blood 2012;119:4275-4282.
26. Alon R, Feigelson SW. Chemokine-triggered leukocyte arrest: force-regulated bi-directional integrin activation in quantal adhesive contacts. Curr Opin Cell Biol 2012;24:670-676.
27. Alon R, Dustin ML. Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen-presenting cells. Immunity 2007;26:17-27.
28. Bolomini-Vittori M, et al. Regulation of conformer-specific activation of the integrin LFA-1 by a chemokine-triggered Rho signaling module. Nat Immunol 2009;10:185-194.
29. Hart R, Stanley P, Chakravarty P, Hogg N. The kindlin 3 pleckstrin homology domain has an essential role in lymphocyte function-associated antigen 1 (LFA-1) integrin-mediated B cell adhesion and migration. J Biol Chem 2013;288:14852-14862.
30. Stanley P, Smith A, McDowall A, Nicol A, Zicha D, Hogg N. Intermediate-affinity LFA-1 binds alpha-actinin-1 to control migration at the leading edge of the T cell. EMBO J 2008;27:62-75.
31. Smith A, Carrasco YR, Stanley P, Kieffer N, Batista FD, Hogg N. A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. J Cell Biol 2005;170:141-151.
32. Smith A, Stanley P, Jones K, Svensson L, McDowall A, Hogg N. The role of the integrin LFA-1 in T-lymphocyte migration. Immunol Rev 2007;218:135-146.
33. Shakhar G, et al. Stable T cell-dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat Immunol 2005;6:707-714.
34. Dustin ML. T-cell activation through immunological synapses and kinapses. Immunol Rev 2008;221:77-89.
35. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998;395:82-86.
36. Grakoui A, et al. The immunological synapse: a molecular machine controlling T cell activation. Science 1999;285:221-227.
37. Dustin ML, Groves JT. Receptor signaling clusters in the immune synapse. Annu Rev Biophys 2012;41:543-556.
38. Babich A, Burkhardt JK. Lymphocyte signaling converges on microtubules. Immunity 2011;34:825-827.
39. Yi J, Wu XS, Crites T, Hammer JA. Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells. Mol Biol Cell 2012;23:834-852.
40. Babich A, Li S, O'Connor RS, Milone MC, Freedman BD, Burkhardt JK. F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation. J Cell Biol 2012;197:775-787.
41. Hammer JA, Burkhardt JK. Controversy and consensus regarding myosin II function at the immunological synapse. Curr Opin Immunol 2013;25:300-306.
42. Dustin ML. The cellular context of T cell signaling. Immunity 2009;30:482-492.
43. Sims TN, et al. Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell 2007;129:773-785.
44. Kim ST, et al. The alphabeta T cell receptor is an anisotropic mechanosensor. J Biol Chem 2009;284:31028-31037.
45. Ilani T, Vasiliver-Shamis G, Vardhana S, Bretscher A, Dustin ML. T cell antigen receptor signaling and immunological synapse stability require myosin IIA. Nat Immunol 2009;10:531-539.
46. Acuto O, Di Bartolo V, Michel F. Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nat Rev Immunol 2008;8:699-712.
47. Stachowiak JC, et al. Membrane bending by protein-protein crowding. Nat Cell Biol 2012;14:944-949.
48. James JR, Vale RD. Biophysical mechanism of T-cell receptor triggering in a reconstituted system. Nature 2012;487:64-69.
49. Allard JF, Dushek O, Coombs D, van der Merwe PA. Mechanical modulation of receptor-ligand interactions at cell-cell interfaces. Biophys J 2012;102:1265-1273.
50. Shyy JY-J, Chien S. Role of integrins in endothelial mechanosensing of shear stress. Circ Res 2002;91:769-775.
51. Moore SW, Roca-Cusachs P, Sheetz MP. Stretchy proteins on stretchy substrates: the important elements of integrin-mediated rigidity sensing. Dev Cell 2010;19:194-206.
52. Chen KD, et al. Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem 1999;274:18393-18400.
53. Astrof NS, Salas A, Shimaoka M, Chen J, Springer TA. Importance of force linkage in mechanochemistry of adhesion receptors. Biochemistry 2006;45:15020-15028.
54. Kong F, García AJ, Mould AP, Humphries MJ, Zhu C. Demonstration of catch bonds between an integrin and its ligand. J Cell Biol 2009;185:1275-1284.
55. Chen W, Lou J, Zhu C. Forcing switch from short- to intermediate- and long-lived states of the alphaA domain generates LFA-1/ICAM-1 catch bonds. J Biol Chem 2010;285:35967-35978.
56. Friedland JC, Lee MH, Boettiger D. Mechanically activated integrin switch controls alpha5beta1 function_sup. Science 2009;323:642-644.
57. Puklin-Faucher E, Vogel V. Integrin activation dynamics between the RGD-binding site and the headpiece hinge. J Biol Chem 2009;284:36557-36568.
58. Puklin-Faucher E, Gao M, Schulten K, Vogel V. How the headpiece hinge angle is opened: new insights into the dynamics of integrin activation. J Cell Biol 2006;175:349-360.
59. Zhu J, Luo B-H, Xiao T, Zhang C, Nishida N, Springer TA. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell 2008;32:849-861.
60. Schwartz MA. Integrins and extracellular matrix in mechanotransduction. Cold Spring Harb Perspect Biol 2010;2:a005066.
61. Li Y-C, et al. Cutting Edge: mechanical forces acting on T cells immobilized via the TCR complex can trigger TCR signaling. J Immunol 2010;184:5959-5963.
62. Bell GI. Models for the specific adhesion of cells to cells. Science 1978;200:618-627.
63. Dembo M, Torney DC, Saxman K, Hammer D. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc R Soc Lond B Biol Sci 1988;234:55-83.
64. Robert P, Aleksic M, Dushek O, Cerundolo V, Bongrand P, van der Merwe PA. Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. Biophys J 2012;102:248-257.
65. Yago T, et al. Platelet glycoprotein Ibalpha forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF. J Clin Invest 2008;118:3195-3207.
66. Yakovenko O, et al. FimH forms catch bonds that are enhanced by mechanical force due to allosteric regulation. J Biol Chem 2008;283:11596-11605.
67. Rakshit S, Zhang Y, Manibog K, Shafraz O, Sivasankar S. Ideal, catch, and slip bonds in cadherin adhesion. Proc Natl Acad Sci USA 2012;109:18815-18820.
68. Guo B, Guilford WH. Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction. Proc Natl Acad Sci USA 2006;103:9844-9849.
69. Akiyoshi B, et al. Tension directly stabilizes reconstituted kinetochore-microtubule attachments. Nature 2010;468:576-579.
70. Lee C-Y, et al. Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds. Proc Natl Acad Sci USA 2013;110:5022-5027.
71. Wu T, Lin J, Cruz MA, Dong J-F, Zhu C. Force-induced cleavage of single VWFA1A2A3 tridomains by ADAMTS-13. Blood 2010;115:370-378.
72. Wiita AP, et al. Probing the chemistry of thioredoxin catalysis with force. Nature 2007;450:124-127.
73. Kim ST, et al. TCR mechanobiology: torques and tunable structures linked to early T cell signaling. Front Immunol 2012;3:76.
74. Davis MM, et al. Ligand recognition by alpha beta T cell receptors. Annu Rev Immunol 1998;16:523-544.
75. Stone JD, Chervin AS, Kranz DM. T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity. Immunology 2009;126:165-176.
76. Huang J, et al. The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness. Nature 2010;464:932-936.
77. Lou J, Zhu C. A structure-based sliding-rebinding mechanism for catch bonds. Biophys J 2007;92:1471-1485.
78. Klopocki AG, et al. Replacing a lectin domain residue in L-selectin enhances binding to P-selectin glycoprotein ligand-1 but not to 6-sulfo-sialyl Lewis x. J Biol Chem 2008;283:11493-11500.
79. Thomas WE, Trintchina E, Forero M, Vogel V, Sokurenko EV. Bacterial adhesion to target cells enhanced by shear force. Cell 2002;109:913-923.
80. Lou J, et al. Flow-enhanced adhesion regulated by a selectin interdomain hinge. J Cell Biol 2006;174:1107-1117.
81. Hogg N, Laschinger M, Giles K, McDowall A. T-cell integrins: more than just sticking points. J Cell Sci 2003;116:4695-4705.
82. Pribila JT, Quale AC, Mueller KL, Shimizu Y. Integrins and T cell-mediated immunity. Annu Rev Immunol 2004;22:157-180.
83. Luo B-H, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol 2007;25:619-647.
84. Xiong J-P, et al. Crystal structure of the extracellular segment of integrin alphaVbeta3. Science 2001;294:339-345.
85. Xiong J-P, et al. Crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with an Arg-Gly-Asp ligand. Science 2002;296:151-155.
86. Xiong J-P, et al. Crystal structure of the complete integrin alphaVbeta3 ectodomain plus an alpha/beta transmembrane fragment. J Cell Biol 2009;186:589-600.
87. Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA. Structure of an integrin with an alphaI domain, complement receptor type 4. EMBO J 2010;29:666-679.
88. Yu Y, et al. Structural specializations of α(4)β(7), an integrin that mediates rolling adhesion. J Cell Biol 2012;196:131-146.
89. Takagi J, Petre BM, Walz T, Springer TA. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 2002;110:599-511.
90. Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer TA. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity 2006;25:583-594.
91. Ye F, et al. Recreation of the terminal events in physiological integrin activation. J Cell Biol 2010;188:157-173.
92. Beglova N, Blacklow SC, Takagi J, Springer TA. Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation. Nat Struct Biol 2002;9:282-287.
93. Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 2003;301:1720-1725.
94. Chigaev A, Buranda T, Dwyer DC, Prossnitz ER, Sklar LA. FRET detection of cellular alpha4-integrin conformational activation. Biophys J 2003;85:3951-3962.
95. Chigaev A, Zwartz GJ, Buranda T, Edwards BS, Prossnitz ER, Sklar LA. Conformational regulation of alpha 4 beta 1-integrin affinity by reducing agents. "Inside-out" signaling is independent of and additive to reduction-regulated integrin activation. J Biol Chem 2004;279:32435-32443.
96. Kim C, Schmidt T, Cho E-G, Ye F, Ulmer TS, Ginsberg MH. Basic amino-acid side chains regulate transmembrane integrin signalling. Nature 2012;481:209-213.
97. Chen W, Lou J, Evans EA, Zhu C. Observing force-regulated conformational changes and ligand dissociation from a single integrin on cells. J Cell Biol 2012;199:497-512.
98. Chen X, Yu Y, Mi L-Z, Walz T, Springer TA. Molecular basis for complement recognition by integrin αXβ2. Proc Natl Acad Sci USA 2012;109:4586-4591.
99. Moser M, Legate KR, Zent R, Fässler R. The tail of integrins, talin, and kindlins. Science 2009;324:895-899.
100. Kim C, Ye F, Hu X, Ginsberg MH. Talin activates integrins by altering the topology of the β transmembrane domain. J Cell Biol 2012;197:605-611.
101. Zhu J, Zhu J, Springer TA. Complete integrin headpiece opening in eight steps. J Cell Biol 2013;201:1053-1068.
102. Zhang F, Marcus WD, Goyal NH, Selvaraj P, Springer TA, Zhu C. Two-dimensional kinetics regulation of alphaLbeta2-ICAM-1 interaction by conformational changes of the alphaL-inserted domain. J Biol Chem 2005;280:42207-42218.
103. Ma Q, Shimaoka M, Lu C, Jing H, Carman CV, Springer TA. Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1. J Biol Chem 2002;277:10638-10641.
104. Litvinov RI, Mekler A, Shuman H, Bennett JS, Barsegov V, Weisel JW. Resolving two-dimensional kinetics of the integrin αIIbβ3-fibrinogen interactions using binding-unbinding correlation spectroscopy. J Biol Chem 2012;287:35275-35285.
105. Horn J, et al. Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa is mandatory for TCR-mediated inside-out signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion, and migration of T cells. J Immunol 2009;183:5756-5767.
106. Lee D, Kim J, Baker RG, Koretzky GA, Hammer DA. SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow. Eur J Immunol 2012;42:2736-2743.
107. Shimaoka M, Lu C, Salas A, Xiao T, Takagi J, Springer TA. Stabilizing the integrin alpha M inserted domain in alternative conformations with a range of engineered disulfide bonds. Proc Natl Acad Sci USA 2002;99:16737-16741.
108. Jin M, Andricioaei I, Springer TA. Conversion between three conformational states of integrin I domains with a C-terminal pull spring studied with molecular dynamics. Structure 2004;12:2137-2147.
109. Xiang X, Lee C-Y, Li T, Chen W, Lou J, Zhu C. Structural basis and kinetics of force-induced conformational changes of an αA domain-containing integrin. PLoS ONE 2011;6:e27946.
110. Woolf E, et al. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat Immunol 2007;8:1076-1085.
111. Shimaoka M, Salas A, Yang W, Weitz-Schmidt G, Springer TA. Small molecule integrin antagonists that bind to the beta2 subunit I-like domain and activate signals in one direction and block them in the other. Immunity 2003;19:391-402.
112. Salas A, Shimaoka M, Kogan AN, Harwood C, Andrian, von, UH, Springer, TA. Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction. Immunity 2004;20:393-406.
113. Shimaoka M, Takagi J, Springer TA. Conformational regulation of integrin structure and function. Annu Rev Biophys Biomol Struct 2002;31:485-516.
114. Xiao T, Takagi J, Coller BS, Wang J-H, Springer TA. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature 2004;432:59-67.
115. Chen W, Lou J, Hsin J, Schulten K, Harvey SC, Zhu C. Molecular dynamics simulations of forced unbending of integrin α(v)β. PLoS Comput Biol 2011;7:e1001086.
116. Burkhardt JK, Carrizosa E, Shaffer MH. The actin cytoskeleton in T cell activation. Annu Rev Immunol 2008;26:233-259.
117. Kishino A, Yanagida T. Force measurements by micromanipulation of a single actin filament by glass needles. Nature 1988;334:74-76.
118. Holmes KC, Popp D, Gebhard W, Kabsch W. Atomic model of the actin filament. Nature 1990;347:44-49.
119. Parekh SH, Chaudhuri O, Theriot JA, Fletcher DA. Loading history determines the velocity of actin-network growth. Nat Cell Biol 2005;7:1219-1223.
120. Schmoller KM, Fernández P, Arevalo RC, Blair DL, Bausch AR. Cyclic hardening in bundled actin networks. Nat Commun 2010;1:134.
121. Kong F, et al. Cyclic mechanical reinforcement of integrin-ligand interactions. Mol Cell 2013;49:1060-1068.
122. Jégou A, Carlier M-F, Romet-Lemonne G. Formin mDia1 senses and generates mechanical forces on actin filaments. Nat Commun 2013;4:1883.
123. Courtemanche N, Lee JY, Pollard TD, Greene EC. Tension modulates actin filament polymerization mediated by formin and profilin. Proc Natl Acad Sci USA 2013;110:9752-9757.
124. Rio AD, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, Sheetz MP. Stretching single talin rod molecules activates vinculin binding. Science 2009;323:638-641.
125. Rossy J, Owen DM, Williamson DJ, Yang Z, Gaus K. Conformational states of the kinase Lck regulate clustering in early T cell signaling. Nat Immunol 2013;14:82-89.
126. Zhang X, Halvorsen K, Zhang C-Z, Wong WP, Springer TA. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor_supplemental. Science 2009;324:1330-1334.
127. Reinherz EL, Acuto O. Molecular T cell biology - basic and translational challenges in the twenty-first century. Front Immunol 2011;2:3.
128. van der Merwe PA, Dushek O. Mechanisms for T cell receptor triggering. Nat Rev Immunol 2011;11:47-55.
129. McKeithan TW. Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 1995;92:5042-5046.
130. Rabinowitz JD, Beeson C, Lyons DS, Davis MM, McConnell HM. Kinetic discrimination in T-cell activation. Proc Natl Acad Sci USA 1996;93:1401-1405.
131. Kersh GJ, Kersh EN, Fremont DH, Allen PM. High- and low-potency ligands with similar affinities for the TCR: the importance of kinetics in TCR signaling. Immunity 1998;9:817-826.
132. Rosette C, 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.
133. Dushek O, Das R, Coombs D. A role for rebinding in rapid and reliable T cell responses to antigen. PLoS Comput Biol 2009;5:e1000578.
134. Valitutti S, Müller S, Cella M, Padovan E, Lanzavecchia A. Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature 1995;375:148-151.
135. Davis SJ, van der Merwe PA. The structure and ligand interactions of CD2: implications for T-cell function. Immunol Today 1996;17:177-187.
136. 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.
137. Davis SJ, van der Merwe PA. The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 2006;7:803-809.
138. Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM. Direct observation of ligand recognition by T cells. Nature 2002;419:845-849.
139. Krogsgaard M, Li Q-J, Sumen C, Huppa JB, Huse M, Davis MM. Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity. Nature 2005;434:238-243.
140. Aivazian D, Stern LJ. Phosphorylation of T cell receptor zeta is regulated by a lipid dependent folding transition. Nat Struct Biol 2000;7:1023-1026.
141. Xu C, et al. Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. Cell 2008;135:702-713.
142. Kuhns MS, et al. Evidence for a functional sidedness to the alphabetaTCR. Proc Natl Acad Sci USA 2010;107:5094-5099.
143. Zhang H, Cordoba S-P, Dushek O, van der Merwe PA. Basic residues in the T-cell receptor ζ cytoplasmic domain mediate membrane association and modulate signaling. Proc Natl Acad Sci USA 2011;108:19323-19328.
144. Stefanová I, Hemmer B, Vergelli M, Martin R, Biddison WE, Germain RN. TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol 2003;4:248-254.
145. Altan-Bonnet G, Germain RN. Modeling T cell antigen discrimination based on feedback control of digital ERK responses. PLoS Biol 2005;3:e356.
146. Ma Z, Sharp KA, Janmey PA, Finkel TH. Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. PLoS Biol 2008;6:e43.
147. Ma Z, Janmey PA, Finkel TH. The receptor deformation model of TCR triggering. FASEB J 2008;22:1002-1008.
148. Mossman KD, Campi G, Groves JT, Dustin ML. Altered TCR signaling from geometrically repatterned immunological synapses. Science 2005;310:1191-1193.
149. Valitutti S, Dessing M, Aktories K, Gallati H, Lanzavecchia A. Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J Exp Med 1995;181:577-584.
150. Sun ZJ, Kim KS, Wagner G, Reinherz EL. Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer. Cell 2001;105:913-923.
151. Natkanski E, Lee W-Y, Mistry B, Casal A, Molloy JE, Tolar P. B cells use mechanical energy to discriminate antigen affinities. Science 2013;340:1587-1590.
152. Puech P-H, Nevoltris D, Robert P, Limozin L, Boyer C, Bongrand P. Force measurements of TCR/pMHC recognition at T cell surface. PLoS ONE 2011;6:e22344.
153. Lim TS, Mortellaro A, Lim CT, Hämmerling GJ, Ricciardi-Castagnoli P. Mechanical interactions between dendritic cells and T cells correlate with T cell responsiveness. J Immunol 2011;187:258-265.
154. Huppa JB, et al. TCR-peptide-MHC interactions in situ show accelerated kinetics and increased affinity. Nature 2010;463:963-967.
155. Sabatino JJ, Huang J, Zhu C, Evavold BD. High prevalence of low affinity peptide-MHC II tetramer-negative effectors during polyclonal CD4 + T cell responses. J Exp Med 2011;208:81-90.
156. Jiang N, et al. Two-stage cooperative T cell receptor-peptide major histocompatibility complex-CD8 trimolecular interactions amplify antigen discrimination. Immunity 2011;34:13-23.
157. Adams JJ, et al. T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. Immunity 2011;35:681-693.
158. Rosenthal KM, et al. Low 2-dimensional CD4 T cell receptor affinity for myelin sets in motion delayed response kinetics. PLoS ONE 2012;7:e32562.
159. Axmann M, Huppa JB, Davis MM, Schütz GJ. Determination of interaction kinetics between the T cell receptor and peptide-loaded MHC class II via single-molecule diffusion measurements. Biophys J 2012;103:L17-9.
160. O'Donoghue GP, Pielak RM, Smoligovets AA, Lin JJ, Groves JT. Direct single molecule measurement of TCR triggering by agonist pMHC in living primary T cells. ELife 2013;2013:e00778.
161. Klotzsch E, Schütz GJ. Improved ligand discrimination by force-induced unbinding of the T cell receptor from peptide-MHC. Biophys J 2013;104:1670-1675.