Cooperative Recognition of MHC Class II:Peptide Complexes by the T Cell Receptor and CD4

  • Dario A. A. Vignali


Since the T cell receptor (TCR) was cloned almost twelve years ago, significant attention has been directed towards understanding the mechanism by which it recognizes its ligand.1,2 For immunoglobulin (Ig), antigen recognition would appear theoretically simple as it invariably binds a single molecule. However, the TCR cannot recognize native proteins and instead foreign antigens must first be processed into short peptides and bound to products of the major histocompatibility complex (MHC) class I or class II loci for presentation to T cells.3–8 Clearly, the TCR must be able to discriminate between its specific ligand combination, and irrelevant peptides bound to the appropriate MHC restriction element or the appropriate peptide bound to another MHC molecule. While this central tenet is the foundation of self:nonself discrimination,9–11 it is unclear whether the TCR can functionally discriminate between MHC molecules and peptide or whether, like immunoglobulin, it recognizes this complex as a single entity.


Peptide Complex Altered Peptide Ligand Cooperative Recognition Peptide Flank Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Davis MM, Bjorkman PJ. T cell antigen receptor genes and T cell recognition. Nature 1988; 334: 395–402.Google Scholar
  2. 2.
    Chein Y-H, Davis MM. How aß T cell receptors `see’ peptide/MHC cornplexes. Immunol Today 1993; 14: 597–602.Google Scholar
  3. 3.
    Rothbard JB, Gefter ML. Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol 1991; 9: 527–65.Google Scholar
  4. 4.
    Bjorkman PJ, Saper MA, Samraoui B et al. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 1987; 329: 506–12.Google Scholar
  5. 5.
    Bjorkman PJ, Saper MA, Samraoui B et al. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 1987; 329: 512–18.Google Scholar
  6. 6.
    Brown JH, Jardetzky TS, Gorga JC et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 1993; 364: 33–39.Google Scholar
  7. 7.
    Babbitt BP, Allen PM, Matsueda GR et al. Binding of immunogenic peptides to Ia histocompatibility molecules. Nature 1985; 317: 359–61.Google Scholar
  8. 8.
    Buus S, Sette A, Grey HM. The interaction between protein-derived immunogenic peptides and Ia. Immunol Rev 1987; 98: 115–41.Google Scholar
  9. 9.
    Katz DH, Hamaoka T, Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med 1973; 137: 1405–18.Google Scholar
  10. 10.
    Rosenthal AJ, Shevach E. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med 1973; 138: 1194–1212.Google Scholar
  11. 11.
    Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 1974; 248: 701–2.Google Scholar
  12. 12.
    Evavold BD, Sloan-Lancaster J, Allen PM. Tickling the TCR: selective T cell functions stimulated by altered peptide ligands. Immunol Today 1993; 14: 602–9.Google Scholar
  13. 13.
    Vignali DAA, Strominger JL. Co-receptor function and the characteristics of MHC-bound peptides: a common link? The Immunologist 1994; 2: 93–99.Google Scholar
  14. 14.
    Janeway CA Jr, Medhzhitov R, Pfeiffer C et al. Altered peptide ligands: conformational changes in the TCR. The Immunologist 1995; 3: 41–44.Google Scholar
  15. 15.
    Janeway CA, Dianzani U, Portoles P et al. Cross-linking and conformational change in T cell receptors: role in activation and in repertiore selection. Cold Spring Harbor Symp Quant Biol 1989; 54: 657–65.Google Scholar
  16. 16.
    Rotzschke O, Falk K. Naturally-occuring peptide antigens derived from the MHC class-I-restricted processing pathway. Immunol Today 1992; 12: 447–55.Google Scholar
  17. 17.
    Urban RG, Chicz RM, Vignali DAA et al. The dichotomy of peptide presentation by class I and class II MHC proteins. In: Sette A, ed. Naturally Processed Peptides. Basel: Karger, 1993: 197–234.Google Scholar
  18. 18.
    Rotzschke O, Falk K, Deres K et al. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 1990; 348: 252–54.Google Scholar
  19. 19.
    Van Bleek GM, Nathenson SG. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2K“ molecule. Nature 1990; 348: 213–16.Google Scholar
  20. 20.
    Rudensky AY, Preston-Hurlburt P, Hong S-C et al. Sequence analysis of peptides bound to MHC class II molecules. Nature 1991; 353: 622–27.Google Scholar
  21. 21.
    Hunt DF, Michel H, Dickinson TA et al. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science 1992; 256: 1817–20.Google Scholar
  22. 22.
    Chicz RM, Urban RG, Lane WS et al. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 1992; 358: 764–68.Google Scholar
  23. 23.
    Chicz RM, Urban RG, Gorga JC et al. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med 1993; 178: 27–47.Google Scholar
  24. 24.
    Pamer EG, Harty JT, Bevan MJ. Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 1991; 353: 852–55.Google Scholar
  25. 25.
    Vignali DAA, Urban RG, Chicz RM et al. Minute quantities of a single immunodominant epitope are presented as large nested sets by MHC class II molecules. Eur J Immunol 1993; 23: 1602–7.Google Scholar
  26. 26.
    Swain S. T cell subsets and the recognition of MHC class. Immunol Rev 1983; 74: 129–42.Google Scholar
  27. 27.
    Parnes JR. Molecular biology and function of CD4 and CD8. Adv Immunol 1989; 44: 265.Google Scholar
  28. 28.
    Rudd CE, Trevillyan JM, Dasgupta JD et al. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci 1988; 85: 5190–94.Google Scholar
  29. 29.
    Veillette A, Bookman MA, Horak EM et al. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine protein kinase p56“. Cell 1988; 55: 301–8.Google Scholar
  30. 30.
    Turner JM, Brodsky MH, Irving BA et al. Interaction of the unique N terminal region of tyrosine kinase p56“ with cytoplasmic domains of CD4 and CD8 is mediated by cystein motifs. Cell 1990; 60: 755–65.Google Scholar
  31. 31.
    Xu H, Littman DR. A kinase-independent function of lck in potentiating antigen-specific T cell activation. Cell 1993; 74: 633–43.Google Scholar
  32. 32.
    Janeway CA Jr. T cell development: accessories or coreceptors? Nature 1988; 335: 208.Google Scholar
  33. 33.
    Janeway CA Jr, Rojo J, Saizawa K et al. The co-receptor function of murine CD4. Immunol Rev 1989; 109: 77–92.Google Scholar
  34. 34.
    Dalgleish AG, Beverley PCL, Clapham PR et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312: 763–67.Google Scholar
  35. 35.
    Klatzmann D, Barre-Sinoussi F, Nugeyre MT et al. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science 1984; 225: 59–63.Google Scholar
  36. 36.
    Travers P. One hand clapping. Nature 1990; 348: 393.Google Scholar
  37. 37.
    Boursier JP, Alcover A, Herve F et al. Evidence for an extended structure of the T cell co-receptor CD8a as deduced from the hydrodynamic properties of soluble forms of the extracellular region. J Biol Chem 1993; 268: 2013–20.Google Scholar
  38. 38.
    Kwong PD, Ryu S-E, Hendrickson WA et al. Molecular characteristics of recombinant human CD4 as deduced from polymorphic crystals. Proc Natl Acad Sci 1990; 87: 6423–27.Google Scholar
  39. 39.
    Wang J, Yan Y, Garrett TPJ et al. Atomic structure of a fragment of human CD4 containing two immunoglobulin like domains. Nature 1990; 348: 411.Google Scholar
  40. 40.
    Ryu SE, Kwong PD, Truneh A et al. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature 1990; 348: 419–26.Google Scholar
  41. 41.
    Brady RL, Dodson EJ, Dodson GG et al. Crystal structure of domains 3 and 4 of rat CD 4: relation to the NH2-terminal domains. Science 1993; 260: 979–83.Google Scholar
  42. 42.
    Leahy DJ, Axel R, Hendrickson WA. Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6A resolution. Cell 1992; 68: 1145–62.Google Scholar
  43. 43.
    Vignali DAA, Doyle C, Kinch MS et al. Interactions of CD4 with MHC class II molecules, T cell receptors and p56’. Phil Trans R Soc Lond 1993; 342: 13–24.Google Scholar
  44. 44.
    Chothia C, Boswell DB, Lesk AM. The outline structure of the T cell aß receptor. EMBO J 1988; 7: 3745–55.Google Scholar
  45. 45.
    Jorgensen JL, Reay PA, Ehrich EW et al. Molecular components of T cell recognition. Annu Rev Immunol 1992; 10: 835–73.Google Scholar
  46. 46.
    Jorgensen JL, Esser U, Fazekas de St. Groth B et al. Mapping T cell receptor-peptide contacts by variant peptide immunization of single chain transgenics. Nature 1992; 355: 224–30.Google Scholar
  47. 47.
    Hong S-C, Chelouche A, Lin R-H et al. An MHC interaction site maps to the amino-terminal half of the T cell receptor a chain variable domain. Cell 1992; 69: 999–1009.Google Scholar
  48. 48.
    Davis MM, Chien Y. Topology and affinity of T cell receptor mediated recognition of peptide-MHC complexes. Curr Opin Immunol 1993; 5: 45–49.Google Scholar
  49. 49.
    Wucherpfennig KW, Hafler DA, Strominger JL. Structure of human T cell receptors specific for an immunodominant myelin basic protein peptide: positioning of T cell receptors on HLA-DR2/peptide complexes. Proc Natl Acad Sci 1995; 92: 8896–8900.Google Scholar
  50. 50.
    Ostrov D, Brawley J, Wright J et al. Restricted T cell receptor usage in response to a peptide antigen, HA 307–319, presented by five different allelic DR molecules: implications for the rotational orientation of the TCR and HLA-DR. 1995. In press.Google Scholar
  51. 51.
    Rahemtulla A, Fung-Leung WP, Schilham M et al. Normal development and function of CD8* cells but markedly decreased helper cell activity in mice lacking CD4. Nature 1991; 353: 180–84.Google Scholar
  52. 52.
    Killeen N, Sawada S, Littman DR. Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4. EMBO J 1993; 12: 1547–53.Google Scholar
  53. 53.
    Clayton LK, Sieh M, Piuous DA et al. Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. Nature 1989; 339: 548–51.Google Scholar
  54. 54.
    Fleury S, Lamarre D, Meloche S et al. Mutational analysis of the interaction between CD4 and class II MHC, class II antigens contact CD4 on a surface opposite the gp120 binding site. Cell 1991; 66: 1037.Google Scholar
  55. 55.
    Moebius U, Clayton LK, Abraham S et al. Human immunodeficiency virus gp120 binding C’C“ ridge of CD4 domain 1 is also involved in the interaction with major histocompatibility complex molecules. PNAS 1992; 89: 12008–12.Google Scholar
  56. 56.
    Vignali DAA. The interaction between CD4 and MHC class II molecules and its effect on T cell function. Behring Inst Mit 1994; 94: 133–47.Google Scholar
  57. 57.
    Stern LJ, Wiley DC. Antigenic peptide binding by class I and class II histocompatibility proteins. Structure 1994; 2: 245–51.Google Scholar
  58. 58.
    Fremont DH, Matsumura M, Stura EA et al. Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science 1992; 257: 919–27.Google Scholar
  59. 59.
    Madden DR, Gorga JC, Strominger JL et al. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 1991; 353: 321–25.Google Scholar
  60. 60.
    Matsumura M, Fremont DH, Peterson PA et al. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 1992; 257: 927–34.Google Scholar
  61. 61.
    Stern LJ, Brown JH, Jardetzky TS et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994; 368: 215–21.Google Scholar
  62. 62.
    Vignali DAA, Strominger JL. Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor. J Exp Med 1994; 179: 1945–56.Google Scholar
  63. 63.
    Allen PM, Matsueda GR, Evans RJ et al. Identification of the T cell and la contact residues of a T cell antigenic epitope. Nature 1987; 327: 713–15.Google Scholar
  64. 64.
    Srinivasan M, Domanico SZ, Kaumaya PTP et al. Peptides of 23 residues or greater are required to stimulate a high affinity class II-restricted T cell response. Eur J Immunol 1993; 23: 1011–16.Google Scholar
  65. 65.
    Harding CV, Unanue ER. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T cell stimulation. Nature 1990; 346: 574–76.Google Scholar
  66. 66.
    Demotz S, Grey HM, Sette A. The minimal number of class II MHCantigen complexes needed for T cell activation. Science 1990; 249: 1028–30.Google Scholar
  67. 67.
    Christinck ER, Luscher MA, Barber BH et al. Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature 1991; 352: 67–69.Google Scholar
  68. 68.
    Schneck J, Maloy WL, Coligan JE et al. Inhibition of an allospecific T cell hybridoma by soluble class I proteins and peptides: estimation of the affinity of a T cell receptor for MHC. Cell 1989; 56: 47–55.Google Scholar
  69. 69.
    Matsui K, Boniface JJ, Reay PA et al. Low affinity interaction of peptideMHC complexes with T cell receptors. Science 1991; 254: 1788–91.Google Scholar
  70. 70.
    Weber S, Traunecker A, Oliveri F et al. Specific low-affinity interaction of major histocompatibility complex plus peptide by soluble T cell receptor. Nature 1992; 356: 793.Google Scholar
  71. 71.
    Sykulev Y, Brunmark A, Tsomides TJ et al. High-affinity reactions between antigen-specific T cell receptors and peptides associated with allogenic and syngeneic major histocompatibility complex class I proteins. Proc Natl Acad Sci 1994; 91: 11487–91.Google Scholar
  72. 72.
    Corr M, Slanetz AE, Boyd LF et al. T cell receptor-MHC class I peptide interactions: affinity, kinetics and specificity. Science 1994; 265: 946–48.Google Scholar
  73. 73.
    Matsui K, Boniface JJ, Steffner P et al. Kinetics of T cell receptor binding to peptide/I-Ek complexes: corrolation of the dissociation rate with T cell responsiveness. Proc Natl Acad Sci 1994; 91: 12862–66.Google Scholar
  74. 74.
    Sykulev Y, Brunmark A, Jackson M et al. Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes. Immunity 1994; 1: 15–22.Google Scholar
  75. 75.
    Davis MM. T cell receptor gene diversity and selection. Annu Rev Biochem 1990; 59: 475–96.Google Scholar
  76. 76.
    Ashton-Rickardt PG, Bandeira A, Delaney JR et al. Evidence for a differential avidity model of T cell selection in the thymus. Cell 1976; 76: 651–63.Google Scholar
  77. 77.
    Sebzda E, Wallace VA, Mayer J et al. Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 1995; 263: 1615–18.Google Scholar
  78. 78.
    Page DM, Alexander J, Snoke K et al. Negative selection of CD4*CD8* thymocytes by T cell receptor peptide antagonists. Proc Natl Acad Sci 1994; 91: 4057–61.Google Scholar
  79. 79.
    Pulendrdran B, Kannourakis G, Nouri S et al. Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. Nature 1995; 375: 331–34.Google Scholar
  80. 80.
    Shokat KM, Goodnow CC. Antigen-induced B cell death and elimination during germinal-centre immune responses. Nature 1995; 375: 334–38.Google Scholar
  81. 81.
    van der Merwe P, Barclay AN. Transient intracellular adhesion: the importance of weak protein-protein interactions. TIBS 1994; 19: 354–58.Google Scholar
  82. 82.
    Karjalainen K. High sensitivity, low affinity-paradox of T cell receptor recognition. Curr Opin Immunol 1994; 6: 9–12.Google Scholar
  83. 83.
    Weiss A. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. Cell 1993; 73: 209–12.Google Scholar
  84. 84.
    Weiss A, Littman DR. Signal transduction by lymphocyte antigen receptors. Cell 1994; 76: 263–74.Google Scholar
  85. 85.
    Valitutti S, Muller S, Cella M et al. Serial triggering of many T cell receptors by a few peptide-MHC complexes. Nature 1995; 375: 148–50.Google Scholar
  86. 86.
    Fantl WJ, Johnson DE, Williams LT. Signalling by receptor tyrosine kinases. Annu Rev Biochem 1993; 62: 453–81.Google Scholar
  87. 87.
    Kornfeld S. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem 1992; 61: 307–30.Google Scholar
  88. 88.
    Krangel MS. Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. J Exp Med 1987; 165: 1141–59.Google Scholar
  89. 89.
    Minami Y, Samelson LE, Klausner RD. Internalization and cycling of the T cell antigen receptor. J Biol Chem 1987; 262: 13342–47.Google Scholar
  90. 90.
    Luton F, Buferne M, Davoust J et al. Evidence for protein tyrosine kinase involvement in ligand-induced TCR/CD3 internalization and surface redistribution. J Immunol 1994; 153: 63–72.Google Scholar
  91. 91.
    Dietrich J, Hou X, Wegener A-MK et al. CD3y contains a phosphoserinedependent di-leucine motif involved in downregulation of the T cell receptor. EMBO J 1994; 13: 2156–66.Google Scholar
  92. 92.
    Cantrell DA, Davis AA, Crumpton MJ. Activators of protein kinase C downregulate and phosphorylate the T3/T cell antigen receptor complex of human T lymphocytes. Proc Natl Acad Sci 1985; 82: 8158–62.Google Scholar
  93. 93.
    Reth M. Antigen receptor tail clue. Nature 1987; 38: 383–84.Google Scholar
  94. 94.
    Canfield WM, Johnson KF, Ye RD et al. Localization of the signal for rapid internalization of the bovine cation-independent mannose 6-phosphate/insulin-like growth factor-II receptor to amino acids 24–29 of the cytoplasmic tail. J Biol Chem 1991; 266: 5682–88.Google Scholar
  95. 95.
    Jadot M, Canfield WM, Gregory W et al. Characterization of the signal for rapid internalization of the bovine mannose 6-phaosphate/insulin-like growth factor-II receptor. J Biol Chem 1992; 267: 11069–77.Google Scholar
  96. 96.
    Emmrich F. Cross-linking of CD4 and CD8 with the T cell receptor complex: quaternary complex formation and T cell repertoire selection. Immunol Today 1988; 9: 296–300.Google Scholar
  97. 97.
    Davis MM. Serial engagement proposed. Nature 1995; 375: 104.Google Scholar
  98. 98.
    Kolanus W, Romeo C, Seed B. T cell activation by clustered tyrosine kinases. Cell 1993; 74: 171–83.Google Scholar
  99. 99.
    Rao A, Ko WW-P, Faas SJ et al. Binding of antigen in the absence of histocompatibility proteins by arsonate-reactive T cell clones. Cell 1984; 36: 879–88.Google Scholar
  100. 100.
    Symer DE, Dintzis RZ, Diamond DJ et al. Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluable antigen arrays. J Exp Med 1992; 176: 1421–30.Google Scholar
  101. 101.
    Letourneur F, Klausner RD. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3e. Science 1991; 255: 79–82.Google Scholar
  102. 102.
    Irving B, Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell 1991; 64: 891–901.Google Scholar
  103. 103.
    Schafer PH, Pierce SK. Evidence for dimers of MHC class II molecules in B lymphocytes and their role in low affinity T cell responses. Immunity 1994; 1: 699–707.Google Scholar
  104. 104.
    Kupfer A, Singer SJ. Cell biology of cytotoxic and helper T cell functions: immunofluorescence microscopic studies of single cells and cell couples. Annu Rev Immunol 1989; 7: 309–37.Google Scholar
  105. 105.
    Stanfield RL, Takimoto-Kamimura M, Rini JM et al. Major antigen-induced domain rearrangements in an antibody. Structure 1993; 1: 83–89.Google Scholar
  106. 106.
    Arlaud GJ, Thielens NM, Illy C. Assembly of the Cl complex. Behring Inst Mit 1993; 93: 189–95.Google Scholar
  107. 107.
    Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203–12.Google Scholar
  108. 108.
    Smilek DE, Wraith DC, Hodgkinson S et al. A single amino acid change in a myelin basic protein peptide confers the capacity to prevent rather than induce experimental autoimmune encephalomyelitis. PNAS 1991; 88: 9633–37.Google Scholar
  109. 109.
    De Magistris MT, Alexander J, Coggeshall M et al. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell 1992; 68: 625–34.Google Scholar
  110. 110.
    Racioppi L, Rocnchese F, Matis LA et al. Peptide-major histocompatibility complex class II complexes with mixed agonist/antagonist properties provide evidence for ligand-related differences in T cell receptor-dependent intracellular signaling. J Exp Med 1993; 177: 1047–60.Google Scholar
  111. 111.
    Jameson SC, Carbone FR, Bevan MJ. Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricetd cytotoxic T cells. J Exp Med 1993; 177: 1541–50.Google Scholar
  112. 112.
    Evavold BD, Allen PM. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science 1991; 252: 1308–10.Google Scholar
  113. 113.
    Pfeiffer C, Stein J, Southwood S et al. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J Exp Med 1995; 181: 1569–74.Google Scholar
  114. 114.
    Windhagen A, Scholz C, Hollsberg P et al. Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand. Immunity 1995; 2: 373–80.Google Scholar
  115. 115.
    Sloan-Lancaster J, Evavold BD, Allen PM. Induction of T cell anergy by altered T cell-receptor ligand on live antigen-presenting cells. Nature 1993; 363: 156–59.Google Scholar
  116. 116.
    Hogquist KA, Jameson SC, Heath WR et al. T cell receptor antagonist peptides induce positive selection. Cell 1994; 76: 17–27.Google Scholar
  117. 117.
    Jameson SC, Hogquist KA, Bevan MJ. Specificity and flexibility in thymic selection. Nature 1994; 369: 750–52.Google Scholar
  118. 118.
    Yoon ST, Dianzani U, Bottomly K et al. Both high and low avidity antibodies to the T cell receptor can have agonist or antagonist activity. Immunity 1995; 1: 563–69.Google Scholar
  119. 119.
    O’Rourke AM, Mescher MF, Webb SR. Activation of polyphosphoinositide hydorolysis in T cells by H-2 alloantigen but not MLS determinants. Science 1990; 249: 171–74.Google Scholar
  120. 120.
    Cho EA, Riley MP, Sillman AL et al. Altered protein tyrosine phosphorylation in anergic Thl cells. J Immunol 1993; 151: 20–28.Google Scholar
  121. 121.
    Sloan-Lancaster J, Shaw A, Rothbard J et al. Partial T cell signaling: altered phospho-and lack of ZAP-70 recruitment in APL-induced T cell anergy. Cell 1994; 79: 913–22.Google Scholar
  122. 122.
    Madrenas J, Wange RL, Wang JL et al. phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science 1995; 267: 515–18.Google Scholar
  123. 123.
    Biddison W, Rao P, Talle MA et al. Possible involvement of the T4 molecule in T cell recognition of class II antigens. Evidence from studies of CTL target cell binding. J Exp Med 1983; 156: 1065.Google Scholar
  124. 124.
    Krensky AM, Reiss CS, Mier JW et al. Long term human cytolytic T cell lines allospecific for HLA-DR and antigen are OKT4’. Proc Natl Acad Sci 1982; 79: 2365–69.Google Scholar
  125. 125.
    Swain SL, Dialynas DP, Fitch FW et al. Monoclonal antibody to L3T4 blocks the function of T cells specific for major histocompatibility complex antigens. J Immunol 1984; 132: 1118–23.Google Scholar
  126. 126.
    Golding H, McCluskey J, Munitz TI et al. T cell recognition of a chimaeric class II/class I MHC molecule and the role of L3T4. Nature 1985; 317: 425–27.Google Scholar
  127. 127.
    Gay D, Maddon P, Sekaly R et al. Functional interaction between human T cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature 1987; 328: 626–29.Google Scholar
  128. 128.
    Doyle C, Strominger JL. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 1987; 330: 256–59.Google Scholar
  129. 129.
    Janeway CA Jr. The T cell receptor as a multicomponant signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. Annu Rev Immunol 1992; 10: 645–74.Google Scholar
  130. 130.
    Julius M, Maroun CR, Haughn L. Distinct roles for CD4 and CD8 as co-receptors in antigen receptor signalling. Immunol Today 1993; 14: 177–83.Google Scholar
  131. 131.
    Killeen N, Littman DR. Helper T cell development in the absence of CD4p56“ association. Nature 1993; 364: 729–32.Google Scholar
  132. 132.
    Weber S, Karjalainen K. Mouse CD4 binds MHC class II with extremely low affinity. Intern Immunol 1993; 5: 695–98.Google Scholar
  133. 133.
    Cammarota G, Scheirle A, Takacs B et al. Identification of a CD4 binding site on the 132 domain of HLA-DR molecules. Nature 1992; 356: 799–801.Google Scholar
  134. 134.
    Lamarre D, Ashkenazi A, Fleury S et al. The MHC-binding and gp120binding functions of CD4 are separable. Science 1989; 245: 743–46.Google Scholar
  135. 135.
    Bowman MR, MacFerrin KD, Schreiber SL et al. Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocomparibility complex molecules. Proc Natl Acad Sci 1990; 87: 9052–56.Google Scholar
  136. 136.
    Zhou P, Anderson GD, Savarirayan S et al. Thymic deletion of V1311’, Vl35’ T cells in H-2E negative, HLA-DQJ’ single transgenic mice. J Immunol 1991; 146: 854.Google Scholar
  137. 137.
    Mazerolles FA, Durandy A, Piatier-Tonneau D et al. Immunosuppressive properties of synthetic peptides derived from CD4 and HLA-DR antigens. Cell 1988; 55: 497.Google Scholar
  138. 138.
    Lombardi G, Barber L, Aichinger G et al. Structural analysis of anti-DR1 allorecognition by using DR1/H-2Ek hybrid molecules. Influence of the 132 domain correlates with CD4 dependence. J Immunol 1991; 147: 2034–40.Google Scholar
  139. 139.
    Vignali DAA, Moreno J, Schiller D et al. Species-specific binding of CD4 to the 132 domain of major histocompatibility complex class II molecules. J Exp Med 1992; 175: 925–32.Google Scholar
  140. 140.
    Konig R, Huang LY, Germain RN. MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8. Nature 1992; 356: 796–98.Google Scholar
  141. 141.
    Potter TA, Rajan TV, Dick RF II et al. Substitution at residue 227 of H-2 class I molecules abrogates recognition by CD8-dependent, but not CD8-independent, cytotoxic T lymphocytes. Nature 1989; 337: 73–75.Google Scholar
  142. 142.
    Salter RD, Benjamin RJ, Wesley PK et al. A binding site for the T cell co-receptor CD8 on the a3 domain of HLA-A2. Nature 1990; 345: 41–46.Google Scholar
  143. 143.
    Anderson P, Blue M-L, Schlossman SF. Comodulation of CD3 and CD4. Evidence for a specific association between CD4 and approximately 5% of the CD3:T cell receptor complexes on helper T lymphocytes. J Immunol 1988; 140: 1732–37.Google Scholar
  144. 144.
    Langedijk JPM, Puijk WC, van Hoorn WP et al. Location of CD4 dimerization site explains critical role of CDR3-like region in HIV-1 infection and T cell activation and implies a model for complex of coreceptor-MHC. J Biol Chem 1993; 268: 16875–78.Google Scholar
  145. 145.
    Eichmann K, Jonsson J-I, Falk I et al. Effective activation of resting mouse T lymphocytes by cross-linking submitogenic concentrations of the cell antigen receptor with either Lyt-2 or L3T4. Eur J Immunol 1987; 17: 643–50.Google Scholar
  146. 146.
    Anderson P, Blue M-L, Morimoto C et al. Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. J Immunol 1987; 139: 678–82.Google Scholar
  147. 147.
    Kupfer A, Singer SJ, Janeway CA Jr et al. Co-clustering of CD4 (L3T4) with the T cell receptor is induced by specific direct interaction of helper T cells and antigen presenting cells. Proc Natl Acad Sci 1987; 84: 5888–92.Google Scholar
  148. 148.
    Burgess KE, Odysseos AD, Zalvan C et al. Biochemical identification of a direct physical interaction between the CD4:p56“ and Ti(TCR)/CD3 complexes. Eur J Immunol 1991; 21: 1663–68.Google Scholar
  149. 149.
    Saizawa K, Rojo J, Janeway CA Jr. Evidence for a physical association of CD4 and the CD3:a:13 T cell receptor. Nature 1987; 328: 260–63.Google Scholar
  150. 150.
    Rojo JM, Saizawa K, Janeway CA Jr. Physical association of CD4 and the T cell receptor can be induced by anti-T cell receptor antibodies. Proc Natl Acad Sci 1989; 86: 3311–15.Google Scholar
  151. 151.
    Mittler RS, Goldman SJ, Spitalny GL et al. T cell receptor-CD4 physical association in a murine T cell hybridoma: Induction by antigen receptor ligation. Proc Natl Acad Sci 1989; 86: 8531–35.Google Scholar
  152. 152.
    Chuck RS, Cantor CR, Tse DT. CD4-T cell antigen receptor complexes on human leukemia T cells. PNAS 1990; 87: 5021–25.Google Scholar
  153. 153.
    Collins TL, Uniyal S, Shin J et al. p56’ association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation. J Immunol 1992; 148: 2159–62.Google Scholar
  154. 154.
    Meuer SC, Schlossman SF, Reinherz EL. Clonal analysis of human cytotoxic T lymphocytes: T4’ and T8’ effector cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci 1982; 79: 4395–99.Google Scholar
  155. 155.
    Marrack P, Endres R, Shimonkevitz R et al. The major histocompatibility complex restricted antigen on T cells. II. Role of the L3T4 product. J Exp Med 1983; 158: 1077.Google Scholar
  156. 156.
    Norment AM, Salter RD, Parham P et al. Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature 1988; 336: 79–81.Google Scholar
  157. 157.
    Vignali DAA, Moreno J, Schiller D et al. Does CD4 help to maintain the fidelity of T cell receptor specificity? Intern Immunol 1992; 4: 621–26.Google Scholar
  158. 158.
    Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci 1992; 89: 5547–51.Google Scholar

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© R.G. Landes Company 1996

Authors and Affiliations

  • Dario A. A. Vignali

There are no affiliations available

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