Selection of the T cell repertoire

Annual Review of Immunology

Volumn 17, Issue , 1999, Pages 829-874

  Sebzda, Eric ^a   Mariathasan, Sanjeev ^a   Ohteki, Toshiaki ^a   Jones, Russell ^a   Bachmann, Martin F ^a   Ohashi, Pamela S ^a  

^a PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

Diversity; Negative selection; Peptides; Positive selection; Thymocyte development

Indexed keywords

MAJOR HISTOCOMPATIBILITY ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR;

ANIMAL CELL; APOPTOSIS; CELL MATURATION; GENE TECHNOLOGY; GENETIC SELECTION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; IMMUNE SYSTEM; MAJOR HISTOCOMPATIBILITY COMPLEX; MODEL; MOLECULAR GENETICS; MOLECULAR INTERACTION; MOUSE; NONHUMAN; ONTOGENY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; THYMOCYTE;

ANIMALS; APOPTOSIS; AUTOIMMUNE DISEASES; CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASE; CELL DIFFERENTIATION; CELL SURVIVAL; HUMANS; ISOENZYMES; MAJOR HISTOCOMPATIBILITY COMPLEX; MODELS, BIOLOGICAL; PEPTIDES; PHOSPHOLIPASE C; PHOSPHOLIPASE C GAMMA; RECEPTORS, ANTIGEN, T-CELL; RECEPTORS, TUMOR NECROSIS FACTOR; T-LYMPHOCYTES; TRANSCRIPTION FACTORS;

EID: 0033009891     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.immunol.17.1.829     Document Type: Review

References (293)

1. Boyd RL, Hugo P. 1991. Towards an integrated view of thymopoiesis. Immunol. Today 12:71-79
2. Anderson G, Moore NC, Owen JJ, Jenkinson EJ. 1996. Cellular interactions in thymocyte development. Annu. Rev. Immunol. 14:73-99
3. von Boehmer H, Fehling HJ. 1997. Structure and function of the pre-T cell receptor. Annu. Rev. Immunol. 15:433-52
4. Zuniga-Pflücker JC, Lenardo MJ. 1996. Regulation of thymocyte development from immature progenitors. Curr. Opin. Immunol. 8:215-24
5. Di Santo JP, Rodewald H-R. 1998. In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyle development. Curr. Opin. Immunol. 10:196-207
6. Zinkernagel RM, Doherty PC. 1974. Restriction of in vitro T cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701-2
7. Shearer GM. 1974. Cell mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur. J. Immunol. 4:257
8. Bevan MJ. 1977. In a radiation chimera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature 269:417-18
9. Zinkernagel RM, Callahan GN, Althage A, Cooper S, Klein PA, Klein J. 1978. On the thymus in the differentiation of "H-2 self-recognition" by T cells: Evidence for dual recognition? J. Exp. Med. 147:882-96
10. Zinkernagel RM, Callahan GN, Klein J, Dennert G. 1978. Cytotoxic T cells learn specificity for self H-2 during differentiation in the thymus. Nature 271:251-53
11. Fink PJ, Bevan MJ. 1978. H-2 antigens of the thymus determine lymphocyte specificity. J. Exp. Med. 148:766-75
12. Matzinger P, Zamoyska R, Waldmann H. 1984. Self tolerance is H-2 restricted. Nature 308:738-41
13. Rammensec H-G, Bevan MJ. 1984. Evidence from in vitro studies that tolerance to self antigens is MHC-restricted. Nature 308:741-44
14. Teh HS, Kisielow P, Scott B, Kishi H, Uematsu Y, Blüthmann H, von Boehmer H. 1988. Thymic major histocompatibility complex antigens and the αβ T cell receptor determine the CD4/CD8 phenotype of T cells. Nature 335:229-33
15. Sha WC, Nelson ChA, Newberry RD, Kranz DM, Russell JH, Loh DY. 1988. Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 335:271-74
16. Berg LJ, Pullen AM, Fazekas de StGB, Mathis D, Benoist C, Davis MM. 1989. Antigen/MHC-specific T cells are preferentially exported from the thymus in the presence of their MHC ligand. Cell 58:1035-1046
17. + T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 341:746-49
18. + thymocytes. Nature 333:742-46
19. Sha WC, Nelson CA, Newberry RD, Kranz DM, Russell JH, Loh DY. 1988. Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 336:73-76
20. Kappler JW, Roehm N, Marrack P. 1987. T cell tolerance by clonal elimination in the thymus. Cell 49:273-80
21. Kappler JW, Staerz UD, White J, Marrack P. 1988. Self tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature 332:35-40
22. a-encoded antigens. Nature 332:40-45
23. Nikolic-Zugic J, Bevan MJ. 1990. Role of self-peptides in positively selecting the T-cell repertoire. Nature 344:65-67
24. Bevan MJ, Hünig T. 1981. T cells respond preferentially to antigens that are similar to self H-2. Proc. Natl. Acad. Sci. USA 78:1843-47
25. Singer A, Mizuochi T, Munitz TI, Gress RE. 1986. Role of self antigens in the selection of the developing T cell repertoire. In Progress in Immunology VI, ed. B Cinader, RG Miller, pp. 60-66. Orlando, FL: Academic
26. Jacobs H, von Boehmer H, Melief CJM, Berns A. 1990. Mutations in the major histocompatibility complex class I antigen presenting groove affect both negative and positive selection of T cells. Eur. J. Immunol. 20:2333-37
27. b mutations that involve peptide binding. Proc. Natl. Acad. Sci. USA 87:6186-90
28. Ohashi PS, Zinkernagel RM, Luescher IF, Hengartner H, Pircher H. 1993. Enhanced positive selection of a transgenic TCR by a restriction element that does not permit negative selection. Int. Immunol. 5:131-38
29. + cytolytic T cells. Nature 344:742-46
30. + T cells. Science 248:1227-30
31. + T cells. Cell 71:1205-14
32. + T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture. J. Exp. Med. 177:1469-73
33. + T cells in the thymus. Cell 73:1041-49
34. Schumacher TNM, Ploegh HL. 1994. Are MHC-bound peptides a nuisance for positive selection? Immunity 1:721-23
35. Ashton-Rickardt PG, Tonegawa S. 1994. A differential-avidity model for T-cell selection. Immunol. Today 15:362-66
36. Jameson SC, Hogquist KA, Bevan MJ, 1995. Positive selection of thymocytes. Annu. Rev. Immunol. 13:93-126
37. Williams O, Tanaka Y, Tarazona R, Kioussis D. 1997. The agonist-antagonist balance in positive selection. Immunol. Today 18:121-26
38. Janeway CA Jr. 1998. A tale of two T cells. Immunity 8:391-94
39. Mannie MD. 1991. A unified model for T cell antigen recognition and thymic selection of the T cell repertoire. J. Theor. Biol. 151:169-92
40. Janeway CA. 1993. High fives or hard clasps? Curr. Biol 2:591-93
41. De Magistris MT, Alexander J, Coggeshall M, Altman A, Gaeta FCA, Grey HM, Sette A. 1992. Antigen analog-major histcompatibility complexes act as antagonists of the T cell receptor. Cell 68:625-34
42. Hogquist KA, Jameson SC, Heath WR, Howard JL, Bevan MJ, Carbone FR. 1994. T cell receptor antagonist peptides induce positive selection. Cell 76:17-27
43. Jameson SC, Hogquist KA, Bevan MJ. 1994. Specificity and flexibility in thymic selection. Nature 369:750-52
44. Basson MA, Bommhardt U, Cole MS, Tso JY, Zamoyska R. 1998. CD3 ligation on immature thymocytes generates antagonist-like signals appropriate for CD8 lineage commitment, independently of T cell receptor specificity. J. Exp. Med. 187:1249-60
45. Sloan-Lancaster J, Shaw AS, Rothbard JB, Allen PM. 1994. Partial T cell signaling: altered phospho-zeta and lack of Zap70 recruitment in APL-induced T cell anergy. Cell 79:913-22
46. Madrenas J, Wange RL, Wang JL, Isakov N, Samelson LE, Germain RN. 1995. Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science 267:515-18
47. + T cells in response to antagonist ligands. J. Exp. Med. 184:149-57
48. La Face DM, Couture C, Anderson K, Shih G, Alexander J, Sette A, Mustelin T, Altman A, Grey HM. 1997. Differential T cell signaling induced by antagonist peptide-MHC complexes and the associated phenotypic responses. J. Immunol. 158:2057-64
49. Chau LA, Bluestone JA, Madrenas J. 1998. Dissociation of intracellular signalling pathways in response to partial agonist ligands of the T cell receptor. J. Exp. Med. 187:1699-1709
50. Hemmer B, Stefanova I, Vergelli M, Germain R, Martin R. 1998. Relationships among TCR ligand potency, thresholds for effector function elicitation, and the quality of early signaling events in human T cells. J. Immunol. 160:5807-14
51. Elliott JI. 1997. T cell repertoire formation displays characteristics of qualitative models of thymic selection. Eur. J. Immunol. 27:1831-37
52. Williams O, Tarazona R, Kioussis D, Harker N, Roderick K. 1998. Interactions with multiple peptide ligands determine the fate of developing thymocytes. Proc. Natl. Acad. Sci. USA 95:5706-11
53. + thymocytes by T-cell receptor peptide antagonists. Proc. Natl. Acad. Sci. USA 91:4057-61
54. Williams O, Tanaka Y, Bix M, Murdjeva M, Littman DR, Kioussis D. 1996. Inhibition of thymocyte negative selection by T cell receptor antagonist peptides. Eur. J. Immunol. 26:532-38
55. Spain LM, Jorgensen JL, Davis MM, Berg LJ. 1994. A peptide antigen antagonist prevents the differentiation of T cell receptor transgenic thymocytes. J. Immunol. 152:1709-17
56. Ignatowicz L, Kappler J, Parker DC, Marrack P. 1996. The responses of mature T cells are not necessarily antagonized by their positively selecting peptide. J. Immunol 157:1827-31
57. Nakano N, Rooke R, Benoist C, Mathis D. 1997. Positive selection of T cells induced by virus-mediated delivery of neo-peptides to the thymus. Science 275:678-83
58. Smyth LA, Williams O, Huby RDJ, Norton T, Acuto O, Ley SC, Kioussis D. 1998. Altered peptide ligands induce quantitatively but not qualitatively different intracellular signals in primary thymocytes. Proc. Natl Acad. Sci. USA 95:8193-98
59. Preckel T, Grimm R, Martin S, Weltzien HU. 1997. Altered hapten ligands antagonize trinitrophenyl-specific cytotoxic T cells and block internalization of hapten-specific receptors. J. Exp. Med. 185:1803-13
60. Bachmann MF, Oxenius A, Speiser DE, Mariathasan S, Hengartner H, Zinkernagel RM, Ohashi PS. 1997. Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. Eur. J. Immunol. 27:2195-2203
61. Bachmann MF, Speiser DE, Zakarian A, Ohashi PS. 1998. Inhibition of TCR-triggering by a spectrum of altered peptide ligands suggests the mechanism for TCR-antagonism. Eur. J. Immunol. In press
62. Valitutti S, Muller S, Cella M, Padovan E, Lanzavecchia A. 1995. Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature 375:148-51
63. Valitutti S, Muller S, Dessing M, Lanzavecchia A. 1996. Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J. Exp. Med. 183:1917-21
64. Sprent J, Lo D, Gao E, Ron Y. 1988. T cell selection in the thymus. Immunol. Rev. 101:173-90
65. King LB, Vacchio MS, Dixon K, Hunziker R, Marguties DH, Ashwell JD. 1995. A targeted glucocorticoid receptor antisense transgene increases thymocyte apoptosis and alters thymocyte development. Immunity 3:647-56
66. Vacchio MS, Ashwell JD. 1997. Thymus-derived glucocorticoids regulate antigen-specific positive selection. J. Exp. Med. 185:2033-38
67. Ashton-Rickardt PG, Bandeira A, Delaney JR, Van Kaer L, Pircher HP, Zinkernagel RM, Tonegawa S. 1994. Evidence for a differential avidity model of T cell selection in the thymus. Cell 76:651-63
68. Sebzda E, Wallace VA, Mayer J, Yeung RSM, Mak TW, Ohashi PS. 1994. Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 263:1615-18
69. + thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus. Immunity 6:401-10
70. d resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo. Immunity 7:233-41
71. Sebzda E, Kündig TM, Thomson CT, Aoki K, Mak SY, Mayer J, Zamborelli TM, Nathenson S, Ohashi PS. 1996. Mature T cell reactivity altered by a peptide agonist that induces positive selection. J. Exp. Med. 183:1093-1104
72. Delaney JR, Sykulev Y, Eisen HN, Tonegawa S. 1998. Differences in the level of expression of class I major histocompatibility complex proteins on thymic epithelial and dendritic cells influence the decision of immature thymocytes between positive and negative selection. Proc. Natl. Acad. Sci. USA 95:5235-40
73. Alam SM, Travers PJ, Wung JL, Nasholds W, Redpath S, Jameson SC, Gasciogne NRJ. 1996. T-cell-receptor affinity and thymocyte positive selection. Nature 381:616-20
74. Motyka B, Teh H-S. 1998. Naturally occurring low affinity peptide/MHC class I ligands can mediate negative selection and T cell activation. J. Immunol. 160:77-86
75. + T cells. Immunity 3:78-86
76. Girao C, Hu Q, Sun J, Ashton-Rickardt PG. 1997. Limits to the differential avidity model of T cell selection in the thymus. J. Immunol. 159:4205-11
77. Chidgey A, Boyd R. 1997. Agonist peptide modulates T cell selection thresholds through qualitative and quantitative shifts in CD8 co-receptor expression. Int. Immunol. 9:1527-36
78. Wang R, Nelson A, Kimachi K, Grey HM, Farr AG. 1998. The role of peptides in thymic positive selection of class II major histocompatibility complex-restricted T cells. Proc. Natl. Acad. Sci. USA 95:3804-9
79. 2+ flux correlates with thymocyte selection. J. Immunol. 161:6030-37
80. Shores EW, Tran T, Grinberg A, Sommers CL, Shen H, Love PE. 1997. Role of the multiple T cell receptor (TCR)-ζ chain signaling motifs in selection of the T cell repertoire. J. Exp. Med. 185:893-900
81. Yamazaki T, Arase H, Ono S, Ohno H, Watanabe H, Saito T. 1997. A shift from negative to positive selection of autoreactive T cells by the reduced level of TCR signal in TCR-transgenic CD3-deficient mice. J. Immunol. 158:1634-40
82. Liu C-P, Crawford F, Marrack P, Kappler J. 1998. T cell positive selection by a high density, low affinity ligand. Proc. Natl. Acad. Sci. USA 95:4522-26
83. Hogquist KA, Tomlinson AJ, Kieper WC, McGargill MA, Hart MC, Naylor S, Jameson SC. 1997. Identification of a naturally occurring ligand for thymic positive selection. Immunity 6:389-99
84. Hu Q, Bazemore Walker CR, Girao C, Opferman JT, Sun J, Shabanowitz J, Hunt DF, Ashton-Rickardt PG. 1997. Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lmphocytes. Immunity 7:221-31
85. Bachmann MF, Ohashi PS. 1998. The role of T cell receptor dimerization in T cell activation. Submitted
86. Bäckström BT, Müller U, Hausmann B, Palmer E. 1998. Positive selection through a motif in the αβ T cell receptor. Science 281:835-38
87. Cantrell D. 1996. T cell antigen receptor signal transduction pathways. Annu. Rev. Immunol. 14:259-74
88. Wange RL, Samelson LE. 1996. Complex complexes: Signaling at the TCR. Immunity 5:197-205
89. Okumura M, Thomas ML. 1995. Regulation of immune function by protein tyrosine phosphatases. Curr. Opin. Immunol. 7:312-19
90. Qian D, Weiss A. 1997. T cell antigen receptor signal transduction. Curr. Opin. Cell Biol. 9:205-12
91. Reich Z, Boniface JJ, Lyons DS, Borochov N, Wachtel EJ, Davis MM. 1997. Ligand-specific oligomerization of T-cell receptor molecules. Nature 387:617-20
92. Bachmann MF, Salzmann M, Oxenius A, Ohashi PS. 1998. Formation of TCR dimers/trimers as a crucial step for T cell activation. Eur. J. Immunol. 28:2571-79
93. Valitutti S, Muller S, Dessing M, Lanzavecchia A. 1996. Signal extinction and T cell repolarization in T helper cell-antigen-presenting cell conjugates. Eur. J. Immunol 26:2012-16
94. Valitutti S, Lanzavecchia A. 1997. Serial triggering of TCRs: a basis for the sensitivity and specificity of antigen recognition. Immunol. Today 18:299-304
95. André P, Boretto J, Hueber A-O, Régnier-Vigouroux A, Gorvel J-P, Ferrier P, Chavrier P. 1997. A dominant-negative mutant of the Rab5 GTPase enhances T cell signaling by interfering with TCR down-modulation in transgenic mice. J. Immunol. 159:5253-63
96. Valitutti S, Dessing M, Aktories K, Gallati H, Lanzavecchia A. 1995. Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton. J. Exp. Med. 181:577-84
97. Fischer K-D, Yong Y-Y, Nishina H, Tedford K, Marengère LEM, Kozieradzki I, Sasaki T, Starr M, Chan G, Gardener S, Nghiem MP, Bouchard D, Barbacid M, Bernstein A, Penninger JM. 1998. Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Curr. Biol. 8:554-62
98. Holsinger LJ, Graef IA, Swat W, Chi T, Bautista DM, Davidson L, Lewis RS, Alt FW, Crabtree GR. 1998. Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction. Curr. Biol. 8:563-72
99. Tarakhovsky A, Turner M, Schaal S, Mee PJ, Duddy LP, Rajewsky K, Tybulewicz VL. 1995. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 374:467-70
100. Zhang R, Alt F, Davidson L, Orkin SH, Swat W. 1995. Defective signalling through the T-and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature 374:470-73
101. + thymocytes. Nature 374:474-77
102. Turner M, Mee PJ, Walters AE, Quinn ME, Mellor AL, Zamoyska R, Tybulewicz VLJ. 1997. A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes. Immunity 7:451-60
103. Kong Y-Y, Fischer KD, Bachmann MF, Mariathasan S, Kozieradzki I, Nghiem MP, Bouchard D, Bernstein A, Ohashi PS, Penninger JM. 1998. Vav regulates peptide-specific apoptosis in thymocytes. J. Exp. Med. 188:2099-2111
104. Alberola-Ila J, Takaki S, Kerner JD, Perlmutter RM. 1997. Differential signalling by lymphocyte antigen receptors. Annu Rev. Immunol. 15:125-54
105. lck tyrosine kinase activation in T cell receptor-mediated thymic selection. J. Exp. Med. 184:931-43
106. van Oers NS, Lowin-Kropf B, Finlay D, Connolly K, Weiss A. 1996. αß T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases. Immunity 5:429-36
107. Groves T, Smiley P, Cooke MP, Forbush K, Perlmutter RM, Guidos CJ. 1996. Fyn can partially substitute for Lck in T lymphocyte development. Immunity 5:417-28
108. fyn in T cell development and optimal stimulation of T cells by antigen. J. Immunol. 160:5410-19
109. Kishihara K, Penninger J, Wallace VA, Kündig TM, Kawai K, Wakeham A, Timms E, Pfeffer K, Ohashi PS, Thomas ML, Furlonger C, Paige CJ, Mak TW. 1993. Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice. Cell 74:143-56
110. + thymocytes, and in B cell maturation. J. Exp. Med. 183:1707-18
111. Love PE, Shores EW, Johnson MD, Tremblay ML, Lee EJ, Grinberg A, Huang SP, Singer A, Westphal H. 1993. T cell development in mice that lack the ζ chain of the T cell antigen receptor complex. Science 261:918-21
112. Ohno H, Aoe T, Taki S, Kitamura D, Ishida Y, Rajewsky K, Saito T. 1993. Developmental and functional impairment of T cells in mice lacking CD3ζ chains. EMBO J. 12:4357-66
113. Malissen M, Gillet A, Rocha B, Trucy J, Vivier E, Boyer C, Köntgen F, Brun N, Mazza G, Spanopoulou E, Guy-Grand D, Malissen B. 1993. T cell development in mice lacking the CD3-ζ/η gene. EMBO J. 12:4347-55
114. -/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 12:4863-75
115. Shores EW, Ono M, Kawabe T, Sommers CL, Tran T, Lui K, Udey MC, Ravetch J, Love PE. 1998. T cell development in mice lacking all T cell receptor ζ family members (ζ, η, and FcεRIγ). J. Exp. Med. 187:1093-1101
116. Negishi I, Motoyama N, Nakayama K, Senju S, Hatakeyama S, Zhang Q, Chan AC, Loh DY. 1995. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature 376:435-38
117. + thymic selection in humans lacking Zap-70 kinase. Cell 76:947-58
118. Chan AC, Kadlecek TA, Elder ME, Filipovich AH, Kuo W-L, Iwashima M, Parslow TG, Weiss A. 1994. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science 264:1599-1601
119. Elder ME, Lin D, Clever J, Chan AC, Hope TJ, Weiss A, Parslow TG. 1994. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science 264:1596-99
120. Cheng AM, Negishi I, Anderson SJ, Chan AC, Bolen J, Loh DY, Pawson T. 1997. The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signalling. Proc. Natl. Acad. Sci. USA 94:9797-801
121. -/- mice by the Syk protein tyrosine kinase. Immunity 7: 369-77
122. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE. 1998. LAT: The ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92:83-92
123. Weber JR, Orstavik S, Torgersen KM, Danbolt NC, Berg SF, Ryan JC, Tasken K, Imboden JB, Vaage JT. 1998. Molecular cloning of the cDNA encoding pp36, a tyrosine phosphorylated adaptor protein selectively expressed by T cells and natural killer cells. J. Exp. Med. 187:1157-61
124. Liu KQ, Bunnell SC, Gurniak CB, Berg LJ. 1998. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. J. Exp. Med. 187:1721-27
125. Liao XC, Littman DR. 1995. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Immunity 3:757-69
126. ras distinguishes positive and negative selection in thymocytes. EMBO J. 14:276-85
127. O'Shea CC, Crompton T, Rosewell IR, Hayday AC, Owen MJ. 1996. Raf regulates positive selection. Eur. J. Immunol. 26:2350-55
128. Alberola-Ila J, Forbush KA, Seger R, Krebs EG, Perlmutter RM. 1996. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature 373:620-23
129. Alberola-Ila J, Hogquist KA, Swan KA, Revan MJ, Perlmutter RM. 1996. Positive and negative selection invoke distinct signaling pathways. J. Exp. Med. 184:9-18
130. Crompton T, Gilmour KC, Owen MJ. 1996. The MAP kinase pathway controls differentiation from double-negative to double-positive thymocytes. Cell 86:243-51
131. Nakayama K, Nakauchi H. 1993. Cyclosporin A inhibits the decrease of CD4/CD8 expression induced by protein kinase C activation. Int. Immunol. 5:419-26
132. Ohaka Y, Kuwata T, Asada A, Zhao Y, Mukai M, Iwata M. 1997. Regulation of thymocyte lineage commitment by the level of classical protein kinase C activity. J. Immunol. 158:5707-16
133. + thymocytes in vitro. J. Immunol. 154:3636-43
134. Takahama Y, Nakauchi H. 1996. Phorbol ester and calcium ionophore can replace TCR signals that induce positive selection of CD4 T cells. J. Immunol. 157:1508-13
135. Tillinghast JP, Russell JH, Fields LE, Loh DY. 1989. Protein kinase C regulation of terminal deoxynucleotidyl transferase. J. Immunol. 143:2378-83
136. Turka LA, Schatz DG, Oettinger MA, Chun JJM, Gorka C, Lee K, McCormack WT, Thompson CB. 1991. Thymocyte expression of RAG-1 and RAG-2: termination by T cell receptor crosslinking. Science 253:778-81
137. Vasquez NJ, Kane LP, Hedrick SM. 1994. Intracellular signals that mediate thymic negative selection. Immunity 1:45-56
138. Jenkins MK, Schwartz RH, Pardoll DM. 1988. Effects of cyclosporine A onT cell development and clonal deletion. Science 241:1655-58
139. Gao E-K, Lo D, Cheney R, Kanagawa O, Sprent J. 1988. Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature 336:176-79
140. Urdahl KB, Pardoll DM, Jenkins MK. 1994. Cyclosporin A inhibits positive selection and delays negative selection in α-β TCR transgenic mice. J. Immunol. 152:2853-59
141. + thymocytes undergoing thymic selection: Requirement of calcineurin activation for thymic positive selection but not negative selection. J. Exp. Med. 181:927-41
142. + thymocyte negative selection. J. Immunol. 156:4594-601
143. Shi Y, Sahai BM, Green DR. 1989. Cyclosporin A inhibits activation-induced cell death in T cell hybridomas and thymocytes. Nature 339:625-26
144. Zhang W, Zimmer G, Chen JZ, Ladd D, Li E, Alt FW, Wiederrecht G, Cryan J, O'Neill EA, Seidman CE, Abbas AK, Seidman JG. 1996. T cell responses in calcineurin Aα-deficient mice. J. Exp. Med. 183:413-20
145. Xanthoudakis S, Viola JPB, Shaw KTY, Luo C, Wallace JD, Bozza PT, Curran T, Rao A. 1996. An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272:892-95
146. Hodge MR, Ranger AM, Charles de la Brousse F, Hoey T, Grusby MJ, Glimcher LH. 1996. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 4:1-20
147. Yoshida H, Nishina H, Takimoto H, Marengère LEM, Wakeham AC, Bouchard D, Kong Y-Y, Ohteki T, Shahinian A, Bachmann MF, Ohashi PS, Penninger JM, Crabtree GR, Mak TW. 1998. The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity 8:115-24
148. Rincón M, Flavell RA. 1996. Regulation of AP-1 and NFAT transcription factors during thymic selection of T cells. Mol. Cell Biol. 16:1074-84
149. Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, Kündig TM, Amakawa R, Kishihara K, Wakeham A, Potter J, Furlonger CL, Narendran A, Suzuki H, Ohashi PS, Paige CJ, Taniguchi T, Mak TW. 1993. Targeted Disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell 75:83-97
150. + thymocytes. Immunity 7:243-54
151. Shao H, Kono DW, Chen L-Y, Rubin EM, Kaye J. 1997. Induction of the early growth response (Egr) family of transcription factors during thymic selection. J. Exp. Med. 185:731-44
152. Liu Z-G, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA. 1994. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature 367:281-84
153. Woronicz JD, Calnan B, Ngo V, Winoto A. 1994. Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 367:277-81
154. Lee SL, Wesselschmidt RL, Linette GP, Kanagawa O, Russell JH, Milbrandt J. 1995. Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77). Science 269:532-34
155. Calnan BJ, Szychowski S, Chan FKM, Cado D, Winoto A. 1995. A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection. Immunity 3:273-82
156. Zhou T, Cheng J, Yang Z, Liu C, Su X, Bluethmann H, Mountz JD. 1996. Inhibition of Nur77/Nurr1 leads to inefficient clonal delection of self-reactive T cells. J. Exp. Med. 183:1879-92
157. Weih F, Rysek R-P, Chen L, Bravo R. 1996. Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. Proc. Natl. Acad. Sci. USA 93:5533-38
158. Kishimoto H, Sprent J. 1997. Negative selection in the thymus includes semimature T cells. J. Exp. Med. 185:263-71
159. Nagata S, Golstein P. 1995. The fas death factor. Science 267:1449-55
160. Singer GG, Abbas AK. 1994. The Fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1:365-71
161. Sytwu H-K, Liblau RL, McDevitt HO. 1996. The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice. Immunity 5:17-30
162. Castro JE, Listman JA, Jacobson BA, Wang Y, Lopez PA, Ju S, Finn PW, Perkins DL. 1996. Fas modulation of apoptosis during negative selection of thymocytes. Immunity 5:617-27
163. Kishimoto H, Surh CD, Sprent J. 1998. A role for Fas in negative selection of thymocytes in vivo. J. Exp. Med. 187:1427-38
164. Enari M, Talanian RV, Wong WW, Nagata S. 1996. Sequential activation of ICE-like and CPP32-Iike proteases during Fas-mediated apoptosis. Nature 380:723-26
165. Alam A, Braun MY, Hartgers F, Lesage S, Cohen L, Hugo P, Denis F, Sekaly RP. 1997. Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. J. Exp. Med. 186:1503-12
166. Sarin A, Wu M-L, Henkart PA. 1996. Different interleukin-1β converting enzyme (ICE) family protease requirements for the apoptotic death of T lymphocytes triggered by diverse stimuli. J. Exp. Med. 184:2445-50
167. Clayton LK, Ghendler Y, Mizoguchi E, Patch RJ, Ocain TD, Orth K, Bhan AK, Dixit VM, Reinherz EL. 1997. T-cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection. EMBO J. 16:2282-93
168. Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA. 1996. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384:368-72
169. Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, Kägi D, Hakem A, McCurrach M, Khoo W, Kaufman SA, Senaldi G, Howard T, Lowe SW, Mak TW. 1998. Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 12:806-19
170. Page DM, Roberts EM, Peschon JJ, Hedrick SM. 1998. TNF receptor-deficient mice reveal striking differences between several models of thymocyte negative selection. J. Immunol. 160:120-33
171. Amakawa R, Hakem A, Kündig TM, Matsuyama T, Simard JJL, Timms E, Wakeham A, Mittruecker HW, Griesser H, Takimoto H, Schmits R, Shahinian A, Ohashi PS, Penninger JM, Mak TW. 1996. Impaired negative selection of T cells in Hodgkin's disease antigen CD30-deficient mice. Cell 84:551-62
172. Foy TM, Page DM, Waldschmidt TJ, Schoneveld A, Laman JD, Masters SR, Tygrett L, Ledbetter JA, Aruffo A, Claassen E, Xu JC, Flavell RA, Oehen S, Hedrick SM, Noelle RJ. 1995. An essential role for gp39, the ligand for CD40, in thymic selection. J. Exp. Med. 182:1377-88
173. Foy TM, Aruffo A, Bajorath J, Buhlmann JE, Noelle RJ. 1996. Immune regulation by CD40 and its ligand GP39, Annu. Rev. Immunol. 14:591-617
174. + thymocytes. J. Immunol. 152:3254-63
175. Shahinian A, Pfeffer K, Lee KP, Kündig TM, Kishihara K, Wakeham A, Kawai K, Ohashi PS, Thompson CB, Mak TW. 1993. Differential T cell costimulatory requirements in CD28-deficient mice. Science 261:609-12
176. Walunas T, Sperling A, Khattri R, Thompson C, Bluestone J. 1996. CD28 expression is not essential for positive and negative selection of thymocytes or peripheral T cell tolerance. J. Immunol. 156:1006-13
177. Vukmanovic S, Stella G, King PD, Dyall R, Hogquist KA, Harty JT, Nikolic-Zugic J, Bevan MJ. 1994. A positively selecting thymic epithelial cell line lacks costimulatory activity. J. Immunol. 152:3814-23
178. + thymocytes. J. Immunol. 149:3217-24
179. 1. J. Immunol. 151:1868-80
180. + thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can he provided by CD28. J. Exp. Med. 179:709-13
181. + thymocytes by two distinct mechanisms differing in their requirement for CD28 costimulation: implications for negative selection in the thymus. J. Exp. Med. 186:1911-22
182. Amsen D, Kruisbeek AM. 1996. CD28-B7 interactions function to co-stimulate clonal deletion of double-positive thymocytes. Int. Immunol. 8:1927-36
183. Lesage S, Charron J, Winslow G, Hugo P. 1997. Induction of thymocyte deletion by purified single peptide/major histocompatibility complex ligands. J. Immunol. 159:2078-81
184. Kishimoto H, Cai Z, Brunmark A, Jackson MR, Peterson PA, Sprent J. 1996. Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes. J. Exp. Med. 184:531-37
185. Su B, Jacinto E, Hibi M, Kallunko T, Karin M, Ben-Neriah Y. 1994. JNK is involved in signal integration during costimulation of T lymphocytes. Cell 77:727-36
186. Nishina H, Fischer KD, Radvanyi L, Shahinian A, Hakem R, Rubie EA, Bernstein A, Mak TW, Woodgett JR, Penninger JM. 1997. Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3. Nature 385:350-53
187. Swat W, Fujikawa K, Ganiatsas S, Yang D, Xavier RJ, Harris NL, Davidson L, Ferrini R, Davis RJ, Labow MA, Flavell RA, Zon LI, Alt FW. 1998. SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development. Immunity 8:625-34
188. Thomis DC, Berg LJ. 1997. The role of Jak3 in lymphoid development, activation, and signaling. Curr. Opin. Immunol. 9:541-47
189. Saijo K, Park SY, Ishida Y, Arase H, Saito T. 1997. Crucial role of Jak3 in negative selection of self-reactive T cells. J. Exp. Med. 185:351-56
190. DiSanto JP, Guy-Grand D, Fisher A, Tarakhovsky A. 1996. Critical role for the common cytokine receptor γ chain in intrathymic and peripheral T cell selection. J. Exp. Med. 183:1111-18
191. Laufer TM, DeKoning J, Markowitz JS, Lo D, Glimcher LH. 1996. Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature 383:81-85
192. van Meerwijk JPM, Marguerat S, Lees RK, Germain RN, Fowlkes BJ, MacDonald HR. 1997. Quantitative impact of thymic clonal deletion on the T cell repertoire. J. Exp. Med. 185:377-84
193. Ignatowicz L, Kappler J, Marrack P. 1996. The repertoire of T cells shaped by a single MHC/peptide ligand. Cell 84:521-29
194. 0/0 mice. Immunity 7:187-95
195. + T cells. Immunity 7:209-19
196. Merkenschlager M, Graf D, Lovatt M, Bommhardt U, Zamoyska R, Fisher AG. 1997. How many thymocytes audition for selection? J. Exp. Med. 186:1149-58
197. Ohashi PS, Pircher H, Bürki K, Zinkernagel RM, Hengartner H. 1990. Distinct sequence of negative or positive selection implied by thymocyte T cell receptor densities. Nature 346:861-63
198. Borgulya P, Kishi H, Muller U, Kirberg J, von Boehmer H. 1991. Development of the CD4 and CD8 lineage of T cells: instruction versus selection. EMBO J. 10:913-18
199. Guidos CJ, Danska JS, Fathman CG, Weissman IL. 1990. T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages J. Exp. Med. 172:835-45
200. Pircher H, Bürki K, Lang R, Hengartner H, Zinkernagel R. 1989. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342:559-61
201. β-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56:27-35
202. high thymocytes are resistant to peptide/major histocompatibility complex ligand-induced negative selection. Eur. J. Immunol 27:2279-89
203. Marrack P, Ignatowicz L, Kappler JW, Boymel J, Freed JH. 1993. Comparison of peptides bound to spleen and thymus class II. J. Exp. Med. 178:2173-83
204. Ignatowicz L, Rees W, Pacholczyk R, Ignatowicz H, Kushnir E, Kappler J, Marrack P. 1997. T cells can be activated by peptides that are unrelated in sequence to their selecting peptide. Immunity 7:179-86
205. Zerrahn J, Held W, Raulet DH. 1997. The MHC reactivity of the T cell repertoire prior to positive and negative selection. Cell 88:627-36
206. Bevan MJ. 1997. In thymic selection, peptide diversity gives and takes away. Immunity 7:175-78
207. -/- mice overtly react with self-major histocompatibility complex molecules upon restoration of normal surface density of T cell receptor-CD3 complex. J. Exp. Med. 185:707-15
208. Kisielow P, Miazek A. 1995. Positive selection of T cells: rescue from programmed cell death and differentiation require continual engagement of the T cell receptor. J. Exp. Med. 181:1975-84
209. Wilkinson RW, Anderson G, Owen JJT, Jenkinson EJ. 1995. Positive selection of thymocytes involves sustained interactions with the thymic microenvironment. J. Immunol 155:5234-40
210. Schmitt S, Müller K-P, Kyewski BA, 1997. Two separable T cell receptor signals reconstitute positive selection of CD4 lineage T cells in vivo. Eur. J. Immunol. 27:2139-44
211. Engelhard VH. 1994. Structure of peptides associated with class I and class II MHC molecules. Annu. Rev. Immunol. 12:181-207
212. Ohashi PS. 1996. T cell selection and autoimmunity: flexibility and tuning. Curr. Opin. Immunol. 8:808-14
213. Henderson RA, Michel H, Sakaguchi K, Shabanowitz J, Appella E, Hunt DF, Engelhard VH. 1992. HLA-A2. I-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science 255:1264-66
214. Wei ML, Cresswell P. 1992. HLA-A2 molecules in an antigen-processing mutant cell contains signal sequence-derived peptides. Nature 356:443-46
215. Sandberg J, Chambers B, Van Kaer L, Kärre K, Ljunggren H-G. 1996. TAP1-deficient mice select a CD8+ T cell repertoire that displays both diversity and peptide specificity. Eur. J. Immunol. 26:288-93
216. 2-microglobulin, MHC class I-deficient mice. Proc. Natl. Acad. Sci. USA 90:2837-41
217. + T cells in Tap-1 mutant mice. Proc. Natl. Acad. Sci. USA 91:6525-28
218. 2-microglobulin-deficient mice is biased towards reactivity against self-major histocompatibility class I. J. Exp. Med. 179:661-72
219. 2-microglobulin-deficient mice. J. Immunol. 154:47-57
220. Tallquist MD, Weaver AJ, Pease LR. 1998. Degenerate recognition of alloantigenic peptides on a positive-selecting class I molecule. J. Immunol. 160:802-9
221. Miyazaki T, Wolf P, Tourne S, Waltzinger C, Dierich A, Barois N, Ploegh H, Benoist C, Mathis D. 1996. Mice lacking H2-M complexes, enigmatic elements of the MHC Class II peptide-loading pathway. Cell 84:531-41
222. Martin DW, Hicks GG, Mendiaratta SK, Leva HI, Ruley HE, Van Kaer L. 1996. H2-M mutant mice are defective in the peptide loading of Class II molecules, antigen presentation, and T cell repertoire selection. Cell 84:543-50
223. Fung-Leung W-P, Surh CD, Liljedahl M, Pang J, Letrucq D, Peterson A, Webt SR, Karisson L. 1996. Antigen presentation and T cell development in H2-M-deficient mice. Science 271:1278-81
224. Sloan VS, Cameron P, Porter G, Gammon M, Amaya M, Mellins E, Zaller DM. 1995. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375:802-6
225. Denzin LK, Cresswell P. 1995. HLA-DM induces CLIP dissociation from MHC class II αβ dimers and facilitates peptide loading. Cell 82:155-65
226. Sherman MA, Weber DA, Jensen PE. 1995. DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide. Immunity 3:197-205
227. Mathis D, Benoist C, Williams V, Kanter M, McDevitt HO. 1983. Several mechanisms can account for defective Eα gene expression in different mouse haplotypes. Proc. Natl. Acad. Sci. USA 80:273-77
228. Gapin L, Fukui Y, Kanellopoulos J, Sano T, Casrouge A, Malier V, Beaudoing E, Gautheret D, Claverie J-M, Sasazuki T, Kourilsky P. 1998. Quantitative analysis of the T cell repertoire selected by a single peptide-major histocompatibility complex. J. Exp. Med. 187:1871-83
229. Grubin CE, Kovats S, deRoos P, Rudensky AY. 1997. Deficient positive selection of CD4 T cells in mice displaying altered repertoires of MHC class II-bound self-peptides. Immunity 7:197-208
230. Tourne S, Nakano N, Viville S, Benoist C, Mathis D. 1995. The influence of invariant chain on the positive selection of single T cell receptor specificities. Eur. J. Immunol. 25:1851-56
231. Sant'Angelo DB, Waterbury PG, Cohen BE, Martin WD, Kaer LV, Hayday AC, Janeway CA Jr. 1997. The imprint of intrathymic self-peptides on the mature T cell receptor repertoire. Immunity 7:517-24
232. k peptide combination. J. Exp. Med. 186:1441-50
233. Kersh GJ, Allen PM. 1996. Essential flexibility in the T-cell recognition of antigen. Nature 380:495-98
234. Pawlowski TJ, Singleton MD, Loh DY, Berg R, Staerz UD. 1996. Permissive recognition during positive selection. Eur. J. Immunol 26:851-57
235. Bjorkman PJ. 1997. MHC restriction in three dimensions: a view of T cell receptor/ligand interactions. Cell 89:167-70
236. Garcia KC, Degano M, Pease LR, Huang M, Peterson PA, Teyton L, Wilson IA. 1998. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 279:1166-72
237. Ding Y-H, Smith KJ, Garboczi DN, Utz U, Biddison WE, Wiley DC. 1998. Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/tax peptide complex using different TCR amino acids. Immunity 8:403-11
238. Teng M-K, Smolyar A, Tse AGD, Liu J-H, Liu J, Hussey RE, Nathenson SG, Chang H-C, Reiinherz EL, Wang JH. 1998. Crystal structure of the N15 TCR is complex with its peptide/MHC (pMHC) ligand: identification of a common docking topology with substantial variation among different TCR-pMHC complexes. Curr. Biol. 6:409-12
239. Strasser A, Harris AW, Cory S. 1991. Bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 67:889-99
240. Gratiot-Deans J, Merino R, Nunez G, Turka LA. 1994. Bcl-2 expression during T-cell development: Early loss and late return occur at specific stages of commitment to differentiation and survival. Proc. Natl. Acad. Sci. USA 91:10685-89
241. Veis DJ, Sentman CL, Bach EA, Korsmeyer SJ. 1993. Expression of the bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. J. Immunol 151:2546-54
242. Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ. 1993. Bcl-2 deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75:229-40
243. Nakayama KI, Nakayama K, Dustin LB, Loh DY. 1995. T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2 deficient mice. J. Exp. Med. 182:1101-9
244. -/- mice. Cell 89:1011-19
245. Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL. 1997. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Cell 89:1033-41
246. + stage during positive selection and promotes thymocyte differentiation at several control points. Immunity 1:197-205
247. + thymocytes is altered by overexpression of the BCL-2 protooncogene in the thymus. J. Exp. Med. 179:145-53
248. Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ. 1991. Bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67:879-88
249. Strasser A, Harris AW, von Boehmer H, Cory S. 1994. Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene. Proc. Natl. Acad. Sci. USA 91:1376-80
250. Chao DT, Korsmeyer SJ. 1998. BCL-2 family: regulators of cell death. Annu. Rev. Immunol. 16:395-419
251. Brady HJM, Gil-Gomez G, Kirberg J, Berns AJM. 1996. Baxα perturbs T cell development and affects cell cycle entry of T cells. EMBO J. 15:6991-7001
252. Grillot DAM, Merino R, Núñez G. 1995. Bcl-xL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice. J. Exp. Med. 182:1973-83
253. Yang X-F, Weber GF, Cantor H. 1997. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity 7:629-39
254. Henning SW, Galandrini R, Hall A, Cantrell DA. 1997. The GTPase Rho has a critical regulatory role in thymus development. EMBO J. 16:2397-407
255. Muthusamy N, Barton K, Leiden JM. 1995. Defective activation and survival of T cells lacking the Ets-1 transcription factor. Nature 377:639-42
256. Buries J-C, Willerford DM, Grévin D, Davidson L, Camus A, Martin P, Stéhelln D, Alt FW. 1995. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Nature 377:635-38
257. Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin WG Jr, Livingston DM, Orkin SH, Greenberg ME. 1996. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 85:549-61
258. Grossman Z, Singer A. 1996. Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus. Proc. Natl. Acad. Sci. USA 93:14747-52
259. Weiss A, Littman DR. 1994. Signal transduction by lymphocyte antigen receptors. Cell 76:263-74
260. Lee NA, Loh DY, Lacy E. 1992. CD8 surface levels alter the fate of α/β T cell receptor-expressing thymocytes in transgenic mice. J. Exp. Med. 175:1013-25
261. Robey EA, Ramsdell F, Kioussis D. 1992. The level of CD8 expression can determine the outcome of thymic selection. Cell 69:1089-96
262. + cytotoxic T cells requires interactions with class I MHC determinants. Nature 333:180-83
263. Zuniga-Pflücker JC, McCarthy SA, Weston M, Longo DL, Singer A, Kruisbeek AM. 1989. Role of CD4 in thymocyte selection and maturation. J. Exp. Med. 169:2085-96
264. Fung-Leung WP, Schilham MW, Rahemtulla A, Kündig TM, Vollenweider M, Potter J, van Ewijk W, Mak TW. 1991. CD8 is need for development of cytotoxic T cells but not helper T cells. Cell 65:443-49
265. Rahemtulla A, Fung-Leung WP, Schilham MW, Kündig TM, Sambhara SR, Narendran A, Arabian A, Wakeham A, Paige CJ, Zinkernagel RM, Miller RG, Mak TW. 1991. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 353:180-84
266. lck association. Nature 364: 729-32
267. + mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8α chain in mice but not rats. J. Immunol. 160:700-7
268. Tarakhovsky A, Müller W, Rajewsky K. 1994. Lymphocyte populations and immune responses in CD5-deficient mice. Eur. J. Immunol 24:1678-84
269. Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Müller W, Killeen N, Rajewsky K. 1995. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269:535-37
270. Shores EW, Love PE. Personal communication. Submitted
271. Plas DR, Johnson R, Pingel JT, Matthews RJ, Dalton M, Roy G, Chan AC, Thomas ML. 1996. Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling. Science 272: 1173-76
272. Pani G, Fischer K-D, Mlinaric-Rascan I, Siminovitch KA. 1996. Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase. J. Exp. Med. 184:839-52
273. Lorenz U, Ravichandran KS, Burakoff SJ, Neel BG. 1996. Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness. Proc. Natl. Acad. Sci. USA 93: 9624-29
274. Kawai K, Ohashi PS. 1995. Immunological function of a defined T-cell population tolerized to low-affinity self antigens. Nature 374:68-69
275. Nossal GJV. 1994. Negative selection of lymphocytes. Cell 76:229-39
276. Baum H, Davies H, Peakman M. 1996. Molecular mimicry in the MHC: hidden clues to autoimmunity? Immunol. Today 17:64-70
277. Wekerle H, Bradl M, Linington C, Kaab G, Kojima K. 1996. The shaping of the brain-specific T lymphocyte repertoire in the thymus. Immunol. Rev. 149:231-43
278. Fairchild PJ, Wraith DC. 1996. Lowering the tone: mechanisms of immunodominance among epitopes with low affinity for MHC. Immunol. Today 17:80-91
279. Le Douarin N, Corbel C, Bandeira A, Thomas-Vaslin V, Modigliani Y, Coutinho A, Salaün J. 1996. Evidence for a thymus-dependent form of tolerance that is not based on elimination or anergy of reactive T cells. Immunol. Rev. 149:35-53
280. Tolosa E, King LB, Ashwell JD. 1998. Thymocyte glucocorticoid resistance alters positive selection and inhibits autoimmunity and lymphoproliferative disease in MRL-lprllpr mice. Immunity 8:67-76
281. bm12 mice. J. Immunol. 150:4702-12
282. Thomas-Vaslin V, Damotte D, Coltey M, Le Douarin NM, Coutinho A, Salaün J. 1997. Abnormal T cell selection on thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice. Proc. Natl. Acad. Sci. USA 94:4598-603
283. Ohteki T, Nishina H, Hessel A, Sebzda E, Ho S, Hugo P, Penninger J, Ohashi PS. 1998. Positive selection of autoreactive T cells. In preparation 281. Lühder F, Katz J, Benoist C, Mathis D. 1998. Major histocompatibility complex class II molecules can protect from diabetes by positively selecting T cells with additional specificities. J. Exp. Med. 187:379-87
284. Akashi K, Kondo M, Weissman IL. 1998. Two distinct pathways of positive selection for thymocytes. Proc. Natl. Acad. Sci. USA 95:2486-91
285. Dave VP, Cao Z, Browne C, Alarcon B, Fernandez-Miguel G, Lafaille J, De la Hera A, Tonegawa S, Kappes DJ. 1997. CD3δ deficiency arrests development of the αβ but not the γδ T cell lineage. EMBO J. 16:1360-70
286. Shores EW, Huang K, Tran T, Lee E, Grinberg A, Love PE. 1994. Role of TCR ζ chain in T cell development and selection. Science 266:1047-1050
287. fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell 70:741-50
288. fyn. Cell 70:751-63
289. Bhatia SK, Tygrett LT, Grabstein KH, Waldschmidt TJ. 1995. The effect of in vivo IL-7 deprivation on T cell maturation. J. Exp. Med. 181:1399-1409
290. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL. 1994. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180:1955-60
291. lck. Nature 357:161-64
292. Cheng AM, Rowley RB, Pao W, Hayday A, Bolen JB, Pawson T. 1995. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378:303-6
293. Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VLJ. 1995. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378:298-302