Immunologic Research

, 41:267

TCR-MHC docking orientation: natural selection, or thymic selection?

Article

Abstract

T cell receptors (TCR) dock on their peptide-major histocompatibility complex (pMHC) targets in a conserved orientation. Since amino acid sidechains are the foundation of specific protein–protein interactions, a simple explanation for the conserved docking orientation is that key amino acids encoded by the TCR and MHC genes have been selected and maintained through evolution in order to preserve TCR/pMHC binding. Expectations that follow from the hypothesis that TCR and MHC evolved to interact are discussed in light of the data that both support and refute them. Finally, an alternative and equally simple explanation for the driving force behind the conserved docking orientation is described.

Keywords

TCR MHC Coevolution CD8 T cells 

References

  1. 1.
    Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC. Structure of the complex between human T-cell receptor, viralpeptide and HLA-A2. Nature. 1996;384(6605):34–41.Google Scholar
  2. 2.
    Garcia KC, Scott CA, Brunmark A, Carbone FR, Peterson PA, Wilson LA, et al. CD8 enhances formation of stable T-cell receptor/MHC class I molecule complexes. Nature. 1996;384(6609):577–81.PubMedGoogle Scholar
  3. 3.
    Daniel C, Horvath S, Allen PM. A basis for alloreactivity: MHC helical residues broaden peptide recognition by the TCR. Immunity. 1998;8(5):543–52.PubMedGoogle Scholar
  4. 4.
    Garcia KC, Degano M, Pease LR, Huang M, Peterson PA, Teyton L, et al. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science. 1998;279(5354):1166–72.PubMedGoogle Scholar
  5. 5.
    Ding YH, Baker BM, Garboczi DN, Biddison WE, Wiley DC. Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity. 1999;11(1):45–56.PubMedGoogle Scholar
  6. 6.
    Reiser JB, Darnault C, Guimezanes A, Gregoire C, Mosser T, Schmitt-Verhulst AM, et al. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat Immunol. 2000;1(4):291–7.PubMedGoogle Scholar
  7. 7.
    Buslepp J, Wang H, Biddison W, Appella E, Collins EJ. A correlation between TCR Valpha docking on MHC and CD8 dependence: implications for T cell selection. Immunity. 2003;19(4):595–606.PubMedGoogle Scholar
  8. 8.
    Stewart-Jones GB, McMichael AJ, Bell JI, Stuart DI, Jones EY. A structural basis for immunodominant human T cell receptor recognition. Nat Immunol. 2003;4(7):657–63.PubMedGoogle Scholar
  9. 9.
    Jerne NK. The somatic generation of immune recognition. Eur J Immunol. 1971;1(1):1–9.PubMedGoogle Scholar
  10. 10.
    Cohn M. Tritope model of restrictive recognition by the TCR. Trends Immunol. 2003;24(3):127–31.PubMedGoogle Scholar
  11. 11.
    Cohn M. Distinguishing the tritope from the interaction antigen models. Trends Immunol. 2004;25(1):8–9; author reply 9–10.PubMedGoogle Scholar
  12. 12.
    Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001;2(12):919–29.PubMedGoogle Scholar
  13. 13.
    Gutell RR, Noller HF, Woese CR. Higher order structure in ribosomal RNA. EMBO J. 1986;5(5):1111–3.PubMedGoogle Scholar
  14. 14.
    Noller HF, Woese CR. Secondary structure of 16S ribosomal RNA. Science. 1981;212(4493):403–11.PubMedGoogle Scholar
  15. 15.
    Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, et al. Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput Biol. 2006;2(4):e33.PubMedGoogle Scholar
  16. 16.
    Rzhetsky A. Estimating substitution rates in ribosomal RNA genes. Genetics. 1995;141(2):771–83.PubMedGoogle Scholar
  17. 17.
    Moyle WR, Campbell RK, Myers RV, Bernard MP, Han Y, Wang X. Co-evolution of ligand-receptor pairs. Nature. 1994;368(6468):251–5.PubMedGoogle Scholar
  18. 18.
    van Kesteren RE, Tensen CP, Smit AB, van Minnen J, Kolakowski LF, Meyerhof W, et al. Co-evolution of ligand-receptor pairs in the vasopressin/oxytocin superfamily of bioactive peptides. J Biol Chem. 1996;271(7):3619–26.PubMedGoogle Scholar
  19. 19.
    Li A, Sadasivam M, Ding JL. Receptor-ligand interaction between vitellogenin receptor (VtgR) and vitellogenin (Vtg), implications on low density lipoprotein receptor and apolipoprotein B/E. The first three ligand-binding repeats of VtgR interact with the amino-terminal region of Vtg. J Biol Chem. 2003;278(5):2799–806.PubMedGoogle Scholar
  20. 20.
    Robinson J, Waller MJ, Parham P, de Groot N, Bontrop R, Kennedy LJ, et al. IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res. 2003;31(1):311–4.PubMedGoogle Scholar
  21. 21.
    Ohta T. Gene conversion vs point mutation in generating variability at the antigen recognition site of major histocompatibility complex loci. J Mol Evol. 1995;41(2):115–9.PubMedGoogle Scholar
  22. 22.
    Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, et al. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991;352(6336):595–600.PubMedGoogle Scholar
  23. 23.
    Thursz MR, Kwiatkowski D, Allsopp CE, Greenwood BM, Thomas HC, Hill AV. Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med. 1995;332(16):1065–9.PubMedGoogle Scholar
  24. 24.
    Rast JP, Anderson MK, Strong SJ, Luer C, Litman RT, Litman GW. Alpha, beta, gamma, and delta T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity. 1997;6(1):1–11.PubMedGoogle Scholar
  25. 25.
    Li WH, Gouy M, Sharp PM, O’HUigin C, Yang YW. Molecular phylogeny of Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora and molecular clocks. Proc Natl Acad Sci USA. 1990;87(17):6703–7.PubMedGoogle Scholar
  26. 26.
    Mikkelsen TS, Wakefield MJ, Aken B, Amemiya CT, Chang JL, Duke S, et al. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature. 2007;447(7141):167–77.PubMedGoogle Scholar
  27. 27.
    Parra ZE, Baker ML, Hathaway J, Lopez AM, Trujillo J, Sharp A, et al. Comparative genomic analysis and evolution of the T cell receptor loci in the opossum Monodelphis domestica. BMC Genomics. 2008;9:111.PubMedGoogle Scholar
  28. 28.
    Criscitiello MF, Saltis M, Flajnik MF. An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks. Proc Natl Acad Sci USA. 2006;103(13):5036–41.PubMedGoogle Scholar
  29. 29.
    Reiser JB, Gregoire C, Darnault C, Mosser T, Guimezanes A, Schmitt-Verhulst AM, et al. A T cell receptor CDR3beta loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide/MHC class I complex. Immunity. 2002;16(3):345–54.PubMedGoogle Scholar
  30. 30.
    Mazza C, Malissen B. What guides MHC-restricted TCR recognition? Semin Immunol. 2007;19(4):225–35.PubMedGoogle Scholar
  31. 31.
    Hahn M, Nicholson MJ, Pyrdol J, Wucherpfennig KW. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat Immunol. 2005;6(5):490–6.PubMedGoogle Scholar
  32. 32.
    Li Y, Huang Y, Lue J, Quandt JA, Martin R, Mariuzza RA. Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. Embo J. 2005;24(17):2968–79.PubMedGoogle Scholar
  33. 33.
    Ely LK, Beddoe T, Clements CS, Matthews JM, Purcell AW, Kjer-Nielsen L, et al. Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction. Proc Natl Acad Sci USA. 2006;103(17):6641–6.PubMedGoogle Scholar
  34. 34.
    Feng D, Bond CJ, Ely LK, Maynard J, Garcia KC. Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction ‘codon’. Nat Immunol. 2007;8(9):975–83.PubMedGoogle Scholar
  35. 35.
    Dai S, Huseby ES, Rubtsova K, Scott-Browne J, Crawford F, Macdonald WA, et al. Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules. Immunity. 2008;28(3):324–34.PubMedGoogle Scholar
  36. 36.
    Wang C, Bradley P, Baker D. Protein-protein docking with backbone flexibility. J Mol Biol. 2007;373(2):503–19.PubMedGoogle Scholar
  37. 37.
    McBeth C, Seamons A, Pizarro JC, Fleishman SJ, Baker D, Kortemme T, et al. A new twist in TCR diversity revealed by a forbidden alphabeta TCR. J Mol Biol. 2008;375(5):1306–19.PubMedGoogle Scholar
  38. 38.
    Sim BC, Wung JL, Gascoigne NR. Polymorphism within a TCRAV family influences the repertoire through class I/II restriction. J Immunol. 1998;160(3):1204–11.PubMedGoogle Scholar
  39. 39.
    Jameson SC, Kaye J, Gascoigne NR. A T cell receptor V alpha region selectively expressed in CD4+ cells. J Immunol. 1990;145(5):1324–31.PubMedGoogle Scholar
  40. 40.
    Jameson SC, Nakajima PB, Brooks JL, Heath W, Kanagawa O, Gascoigne NR. The T cell receptor V alpha 11 gene family. Analysis of allelic sequence polymorphism and demonstration of J alpha region-dependent recognition by allele-specific antibodies. J Immunol. 1991;147(9):3185–93.PubMedGoogle Scholar
  41. 41.
    Sim BC, Gascoigne NR. Reciprocal expression in CD4 or CD8 subsets of different members of the V alpha 11 gene family correlates with sequence polymorphism. J Immunol. 1999;162(6):3153–9.PubMedGoogle Scholar
  42. 42.
    Sim BC, Zerva L, Greene MI, Gascoigne NR. Control of MHC restriction by TCR Valpha CDR1 and CDR2. Science. 1996;273(5277):963–6.PubMedGoogle Scholar
  43. 43.
    Sim BC, Lo D, Gascoigne NR. Preferential expression of TCR V alpha regions in CD4/CD8 subsets: class discrimination or co-receptor recognition? Immunol Today. 1998;19(6):276–82.PubMedGoogle Scholar
  44. 44.
    Manning TC, Parke EA, Teyton L, Kranz DM. Effects of complementarity determining region mutations on the affinity of an alpha/beta T cell receptor: measuring the energy associated with CD4/CD8 repertoire skewing. J Exp Med. 1999;189(3):461–70.PubMedGoogle Scholar
  45. 45.
    Correia-Neves M, Waltzinger C, Wurtz JM, Benoist C, Mathis D. Amino acids specifying MHC class preference in TCR V alpha 2 regions. J Immunol. 1999;163(10):5471–7.PubMedGoogle Scholar
  46. 46.
    Eshima K, Suzuki H, Shinohara N. Cross-positive selection of thymocytes expressing a single TCR by multiple major histocompatibility complex molecules of both classes: implications for CD4+ versus CD8+ lineage commitment. J Immunol. 2006;176(3):1628–36.PubMedGoogle Scholar
  47. 47.
    Merkenschlager M, Benoist C, Mathis D. MHC control of the naive TCR alpha-chain repertoire. J Immunol. 1994;153(7):3005–13.PubMedGoogle Scholar
  48. 48.
    Turner SJ, Doherty PC, McCluskey J, Rossjohn J. Structural determinants of T-cell receptor bias in immunity. Nat Rev Immunol. 2006;6(12):883–94.PubMedGoogle Scholar
  49. 49.
    Lim A, Trautmann L, Peyrat MA, Couedel C, Davodeau F, Romagne F, et al. Frequent contribution of T cell clonotypes with public TCR features to the chronic response against a dominant EBV-derived epitope: application to direct detection of their molecular imprint on the human peripheral T cell repertoire. J Immunol. 2000;165(4):2001–11.PubMedGoogle Scholar
  50. 50.
    Casrouge A, Beaudoing E, Dalle S, Pannetier C, Kanellopoulos J, Kourilsky P. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J Immunol. 2000;164(11):5782–7.PubMedGoogle Scholar
  51. 51.
    Penit C, Lucas B, Vasseur F. Cell expansion and growth arrest phases during the transition from precursor (CD4−8−) to immature (CD4+8+) thymocytes in normal and genetically modified mice. J Immunol. 1995;154(10):5103–13.PubMedGoogle Scholar
  52. 52.
    Hamrouni A, Aublin A, Guillaume P, Maryanski JL. T cell receptor gene rearrangement lineage analysis reveals clues for the origin of highly restricted antigen-specific repertoires. J Exp Med. 2003;197(5):601–14.PubMedGoogle Scholar
  53. 53.
    Hughes MM, Yassai M, Sedy JR, Wehrly TD, Huang CY, Kanagawa O, et al. T cell receptor CDR3 loop length repertoire is determined primarily by features of the V(D)J recombination reaction. Eur J Immunol. 2003;33(6):1568–75.PubMedGoogle Scholar
  54. 54.
    Kortemme T, Baker D. A simple physical model for binding energy hot spots in protein-protein complexes. Proc Natl Acad Sci USA. 2002;99(22):14116–21.PubMedGoogle Scholar
  55. 55.
    Adams EJ, Strop P, Shin S, Chien YH, Garcia KC. An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells. Nat Immunol. 2008;9(7):777–84.PubMedGoogle Scholar
  56. 56.
    Blackman M, Yague J, Kubo R, Gay D, Coleclough C, Palmer E, et al. The T cell repertoire may be biased in favor of MHC recognition. Cell. 1986;47(3):349–57.PubMedGoogle Scholar
  57. 57.
    Ignatowicz L, Kappler J, Marrack P. The repertoire of T cells shaped by a single MHC/peptide ligand. Cell. 1996;84(4):521–9.PubMedGoogle Scholar
  58. 58.
    Marrack P, Bender J, Jordan M, Rees W, Robertson J, Schaefer BC, et al. Major histocompatibility complex proteins and TCRs: do they really go together like a horse and carriage? J Immunol. 2001;167(2):617–21.PubMedGoogle Scholar
  59. 59.
    Liu CP, Parker D, Kappler J, Marrack P. Selection of antigen-specific T cells by a single IEk peptide combination. J Exp Med. 1997;186(9):1441–50.PubMedGoogle Scholar
  60. 60.
    Huseby ES, White J, Crawford F, Vass T, Becker D, Pinilla C, et al. How the T cell repertoire becomes peptide and MHC specific. Cell. 2005;122(2):247–60.PubMedGoogle Scholar
  61. 61.
    Woolnough JA, Misko IS, Lafferty KJ. Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro. Aust J Exp Biol Med Sci. 1979;57(5):467–77.PubMedGoogle Scholar
  62. 62.
    Engelhard VH, Le AX, Holterman MJ. Species-specific structural differences in the alpha 1 + alpha 2 domains determine the frequency of murine cytotoxic T cell precursors stimulated by human and murine class I molecules. J Immunol. 1988;141(6):1835–9.PubMedGoogle Scholar
  63. 63.
    Irwin MJ, Heath WR, Sherman LA. Species-restricted interactions between CD8 and the alpha 3 domain of class I influence the magnitude of the xenogeneic response. J Exp Med. 1989;170(4):1091–101.PubMedGoogle Scholar
  64. 64.
    Zerrahn J, Held W, Raulet DH. The MHC reactivity of the T cell repertoire prior to positive and negative selection. Cell. 1997;88(5):627–36.PubMedGoogle Scholar
  65. 65.
    Laouini D, Casrouge A, Dalle S, Lemonnier F, Kourilsky P, Kanellopoulos J. V beta T cell repertoire of CD8+ splenocytes selected on nonpolymorphic MHC class I molecules. J Immunol. 2000;165(11):6381–6.PubMedGoogle Scholar
  66. 66.
    Berg RE, Princiotta MF, Irion S, Moticka JA, Dahl KR, Staerz UD. Positive selection of an H2-M3 restricted T cell receptor. Immunity. 1999;11(1):33–43.PubMedGoogle Scholar
  67. 67.
    Kurepa Z, Su J, Forman J. Memory phenotype of CD8+ T cells in MHC class la-deficient mice. J Immunol. 2003;170(11):5414–20.PubMedGoogle Scholar
  68. 68.
    Seaman MS, Perarnau B, Lindahl KF, Lemonnier FA, Forman J. Response to Listeria monocytogenes in mice lacking MHC class Ia molecules. J Immunol. 1999;162(9):5429–36.PubMedGoogle Scholar
  69. 69.
    Rohrlich PS, Fazilleau N, Ginhoux F, Firat H, Michel F, Cochet M, et al. Direct recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function. Proc Natl Acad Sci USA. 2005;102(36):12855–60.PubMedGoogle Scholar
  70. 70.
    Grusby MJ, Auchincloss H Jr, Lee R, Johnson RS, Spencer JP, Zijlstra M, et al. Mice lacking major histocompatibility complex class I and class II molecules. Proc Natl Acad Sci USA. 1993;90(9):3913–7.PubMedGoogle Scholar
  71. 71.
    Lee RS, Grusby MJ, Laufer TM, Colvin R, Glimcher LH, Auchincloss H Jr. CD8+ effector cells responding to residual class I antigens, with help from CD4+ cells stimulated indirectly, cause rejection of “major histocompatibility complex-deficient” skin grafts. Transplantation. 1997;63(8):1123–33.PubMedGoogle Scholar
  72. 72.
    Merkenschlager M, Graf D, Lovatt M, Bommhardt U, Zamoyska R, Fisher AG. How many thymocytes audition for selection? J Exp Med. 1997;186(7):1149–58.PubMedGoogle Scholar
  73. 73.
    Henderson SC, Berezovskaya A, English A, Palliser D, Rock KL, Bamezai A. CD4+ T cells mature in the absence of MHC class I and class II expression in Ly-6A.2 transgenic mice. J Immunol. 1998;161(1):175–82.PubMedGoogle Scholar
  74. 74.
    Robey E, Itano A, Fanslow WC, Fowlkes BJ. Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice. J Exp Med. 1994;179(6):1997–2004.PubMedGoogle Scholar
  75. 75.
    Swanson PA 2nd, Pack CD, Hadley A, Wang CR, Stroynowski I, Jensen PE, et al. An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med. 2008;205(7):1647–57.PubMedGoogle Scholar
  76. 76.
    Lefranc MP. IMGT, the international ImMunoGeneTics information system(R): a standardized approach for immunogenetics and immunoinformatics. Immunome Res. 2005;1(1):3.PubMedGoogle Scholar
  77. 77.
    Bangham R, Michaud GA, Schweitzer B, Predki PF. Protein microarray-based screening of antibody specificity. Methods Mol Med. 2005;114:173–82.PubMedGoogle Scholar
  78. 78.
    Van Laethem F, Sarafova SD, Park JH, Tai X, Pobezinsky L, Guinter TI, et al. Deletion of CD4 and CD8 coreceptors permits generation of alphabeta T cells that recognize antigens independently of the MHC. Immunity. 2007;27(5):735–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Huseby ES, Kappler JW, Marrack P. Thymic selection stifles TCR reactivity with the main chain structure of MHC and forces interactions with the peptide side chains. Mol Immunol. 2008;45(3):599–606.PubMedGoogle Scholar
  80. 80.
    Marrack P, Scott-Browne JP, Dai S, Gapin L, Kappler JW. Evolutionary conserved amino acids that control TCR-MHC interaction. Annu Rev Immunol. 2008;26:171–203.PubMedGoogle Scholar
  81. 81.
    Coif LA, Bankovich AJ, Hanick NA, Bowerman NA, Jones LL, Kranz DM, et al. How a single T cell receptor recognizes both self and foreign MHC. Cell. 2007;129(1):135–46.Google Scholar
  82. 82.
    Batalia MA, Collins EJ. Peptide binding by class I and class II MHC molecules. Biopolymers. 1997;43(4):281–302.PubMedGoogle Scholar
  83. 83.
    Garcia KC, Adams EJ. How the T cell receptor sees antigen—a structural view. Cell. 2005;122(3):333–6.PubMedGoogle Scholar
  84. 84.
    Miller PJ, Pazy Y, Conti B, Riddle D, Appella E, Collins EJ. Single MHC mutation eliminates enthalpy associated with T cell receptor binding. J Mol Biol. 2007;373(2):315–27.PubMedGoogle Scholar
  85. 85.
    Hutchinson SL, Wooldridge L, Tafuro S, Laugel B, Glick M, Boulter JM, et al. The CD8 T cell coreceptor exhibits disproportionate biological activity at extremely low binding affinities. J Biol Chem. 2003;278(27):24285–93.PubMedGoogle Scholar
  86. 86.
    Pecht I, Gakamsky DM. Spatial coordination of CD8 and TCR molecules controls antigen recognition by CD8+ T-cells. FEBS Lett. 2005;579(15):3336–41.PubMedGoogle Scholar
  87. 87.
    Mallaun M, Naeher D, Daniels MA, Yachi PP, Hausmann B, Luescher IF, et al. The T cell receptor’s alpha-chain connecting peptide motif promotes close approximation of the CD8 coreceptor allowing efficient signal initiation. J Immunol. 2008;180(12):8211–21.PubMedGoogle Scholar
  88. 88.
    Purbhoo MA, Boulter JM, Price DA, Vuidepot AL, Hourigan CS, Dunbar PR, et al. The human CD8 coreceptor effects cytotoxic T cell activation and antigen sensitivity primarily by mediating complete phosphorylation of the T cell receptor zeta chain. J Biol Chem. 2001;276(35):32786–92.PubMedGoogle Scholar
  89. 89.
    Wooldridge L, van den Berg HA, Glick M, Gostick E, Laugel B, Hutchinson SL, et al. Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell receptor-antigen complexes at the cell surface. J Biol Chem. 2005;280(30):27491–501.PubMedGoogle Scholar
  90. 90.
    Wyer JR, Willcox BE, Gao GF, Gerth UC, Davis SJ, Bell JI, et al. T cell receptor and coreceptor CD8 alphaalpha bind peptide-MHC independently and with distinct kinetics. Immunity. 1999;10(2):219–25.PubMedGoogle Scholar
  91. 91.
    Norment AM, Salter RD, Parham P, Engelhard VH, Littman DR. Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature. 1988;336(6194):79–81.PubMedGoogle Scholar
  92. 92.
    Jelonek MT, Classon BJ, Hudson PJ, Margulies DH. Direct binding of the MHC class I molecule H-2Ld to CD8: interaction with the amino terminus of a mature cell surface protein. J Immunol. 1998;160(6):2809–14.PubMedGoogle Scholar
  93. 93.
    Daniels MA, Jameson SC. Critical role for CD8 in T cell receptor binding and activation by peptide/major histocompatibility complex multimers. J Exp Med. 2000;191(2):335–46.PubMedGoogle Scholar
  94. 94.
    Holler PD, Kranz DM. Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation. Immunity. 2003;18(2):255–64.PubMedGoogle Scholar
  95. 95.
    Norment AM, Littman DR. A second subunit of CD8 is expressed in human T cells. Embo J. 1988;7(11):3433–9.PubMedGoogle Scholar
  96. 96.
    Bachmann MF, Oxenius A, Mak TW, Zinkernagel RM. T cell development in CD8−/− mice. Thymic positive selection is biased toward the helper phenotype. J Immunol. 1995;155(8):3727–33.PubMedGoogle Scholar
  97. 97.
    Arcaro A, Gregoire C, Boucheron N, Stotz S, Palmer E, Malissen B, et al. Essential role of CD8 palmitoylation in CD8 coreceptor function. J Immunol. 2000;165(4):2068–76.PubMedGoogle Scholar
  98. 98.
    Bosselut R, Kubo S, Guinter T, Kopacz JL, Altman JD, Feigenbaum L, et al. Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus. Immunity. 2000;12(4):409–18.PubMedGoogle Scholar
  99. 99.
    McNicol AM, Bendle G, Holler A, Matjeka T, Dalton E, Rettig L, et al. CD8alpha/alpha homodimers fail to function as co-receptor for a CD8-dependent TCR. Eur J Immunol. 2007;37(6):1634–41.PubMedGoogle Scholar
  100. 100.
    Turner JM, Brodsky MH, Irving BA, Levin SD, Perlmutter RM, Littman DR. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990;60(5):755–65.PubMedGoogle Scholar
  101. 101.
    Shaw AS, Chalupny J, Whitney JA, Hammond C, Amrein KE, Kavathas P, et al. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase. Mol Cell Biol. 1990;10(5):1853–62.PubMedGoogle Scholar
  102. 102.
    Zamoyska R, Derham P, Gorman SD, von Hoegen P, Bolen JB, Veillette A, et al. Inability of CD8 alpha′ polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo. Nature. 1989;342(6247):278–81.PubMedGoogle Scholar
  103. 103.
    Love PE, Lee J, Shores EW. Critical relationship between TCR signaling potential and TCR affinity during thymocyte selection. J Immunol. 2000;165(6):3080–7.PubMedGoogle Scholar
  104. 104.
    Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, et al. Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature. 1997;387(6633):630–4.PubMedGoogle Scholar
  105. 105.
    Kern PS, Teng MK, Smolyar A, Liu JH, Liu J, Hussey RE, et al. Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-2Kb. Immunity. 1998;9(4):519–30.PubMedGoogle Scholar
  106. 106.
    Chang HC, Tan K, Ouyang J, Parisini E, Liu JH, Le Y, et al. Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer. Immunity. 2005;23(6):661–71.PubMedGoogle Scholar
  107. 107.
    Kwan Lim GE, McNeill L, Whitley K, Becker DL, Zamoyska R. Co-capping studies reveal CD8/TCR interactions after capping CD8β polypeptides and intracellular associations of CD8 with p56lck. Eur J Immunol. 1998;28(2):745–54.PubMedGoogle Scholar
  108. 108.
    Boursier JP, Alcover A, Herve F, Laisney I, Acuto O. Evidence for an extended structure of the T-cell co-receptor CD8 alpha as deduced from the hydrodynamic properties of soluble forms of the extracellular region. J Biol Chem. 1993;268(3):2013–20.PubMedGoogle Scholar
  109. 109.
    Manolios N, Bonifacino JS, Klausner RD. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science. 1990;249(4966):274–7.PubMedGoogle Scholar
  110. 110.
    Backstrom BT, Milia E, Peter A, Jaureguiberry B, Baldari CT, Palmer E. A motif within the T cell receptor alpha chain constant region connecting peptide domain controls antigen responsiveness. Immunity. 1996;5(5):437–47.PubMedGoogle Scholar
  111. 111.
    Naeher D, Luescher IF, Palmer E. A role for the alpha-chain connecting peptide motif in mediating TCR-CD8 cooperation. J Immunol. 2002;169(6):2964–70.PubMedGoogle Scholar
  112. 112.
    Ulivieri C, Peter A, Orsini E, Palmer E, Baldari CT. Defective signaling to Fyn by a T cell antigen receptor lacking the alpha-chain connecting peptide motif. J Biol Chem. 2001;276(5):3574–80.PubMedGoogle Scholar
  113. 113.
    Werlen G, Hausmann B, Palmer E. A motif in the alphabeta T-cell receptor controls positive selection by modulating ERK activity. Nature. 2000;406(6794):422–6.PubMedGoogle Scholar
  114. 114.
    Gagnon SJ, Borbulevych OY, Davis-Harrison RL, Turner RV, Damirjian M, Wojnarowicz A, et al. T cell receptor recognition via cooperative conformational plasticity. J Mol Biol. 2006;363(1):228–43.PubMedGoogle Scholar
  115. 115.
    Ding YH, Smith KJ, Garboczi DN, Utz U, Biddison WE, Wiley DC. Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. Immunity. 1998;8(4):403–11.PubMedGoogle Scholar
  116. 116.
    Chen JL, Stewart-Jones G, Bossi G, Lissin NM, Wooldridge L, Choi EM, et al. Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J Exp Med. 2005;201(8):1243–55.PubMedGoogle Scholar
  117. 117.
    Sami M, Rizkallah P, Dunn S, Molloy P, Moysey R, Vuidepot A, et al. Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry. Protein Eng Des Sel. 2007;20:397–403.PubMedGoogle Scholar
  118. 118.
    Tynan FE, Burrows SR, Buckle AM, Clements CS, Borg NA, Miles JJ, et al. T cell receptor recognition of a ‘super-bulged’ major histocompatibility complex class I-boundpeptide. Nat Immunol. 2005;6(11):1114–22.PubMedGoogle Scholar
  119. 119.
    Kjer-Nielsen L, Clements CS, Brooks AG, Purcell AW, McCluskey J, Rossjohn J. The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance. Structure. 2002;10(11):1521–32.PubMedGoogle Scholar
  120. 120.
    Tynan FE, Reid HH, Kjer-Nielsen L, Miles JJ, Wilce MC, Kostenko L, et al. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat Immunol. 2007;8(3):268–76.PubMedGoogle Scholar
  121. 121.
    Reiser JB, Darnault C, Gregoire C, Mosser T, Mazza G, Kearney A, et al. CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat Immunol. 2003;4(3):241–7.PubMedGoogle Scholar
  122. 122.
    Housset D, Mazza G, Gregoire C, Piras C, Malissen B, Fontecilla-Camps JC. The three-dimensional structure of a T-cell antigen receptor V alpha V beta heterodimer reveals a novel arrangement of the V beta domain. Embo J. 1997;16(14):4205–16.PubMedGoogle Scholar
  123. 123.
    Teng MK, Smolyar A, Tse AG, Liu JH, Liu J, Hussey RE, et al. Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes. Curr Biol. 1998;8(7):409–12.PubMedGoogle Scholar
  124. 124.
    Wang J, Lim K, Smolyar A, Teng M, Liu J, Tse AG, et al. Atomic structure of an alphabeta T cell receptor (TCR) heterodimer in complex with an anti-TCR fab fragment derived from a mitogenic antibody. Embo J. 1998;17(1):10–26.PubMedGoogle Scholar
  125. 125.
    Luz JG, Huang M, Garcia KC, Rudolph MG, Apostolopoulos V, Teyton L, et al. Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions. J Exp Med. 2002;195(9):1175–86.PubMedGoogle Scholar
  126. 126.
    Degano M, Garcia KC, Apostolopoulos V, Rudolph MG, Teyton L, Wilson LA. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity. 2000;12(3):251–61.PubMedGoogle Scholar
  127. 127.
    Hoare HL, Sullivan LC, Pietra G, Clements CS, Lee EJ, Ely LK, et al. Structural basis for a major histocompatibility complex class Ib-restricted T cell response. Nat Immunol. 2006;7(3):256–64.PubMedGoogle Scholar
  128. 128.
    Hennecke J, Carfi A, Wiley DC. Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. Embo J. 2000;19(21):5611–24.PubMedGoogle Scholar
  129. 129.
    Hennecke J, Wiley DC. Structure of a complex of the human alpha/beta T cell receptor (TCR) HA 1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB 1*0401): insight into TCR cross-restriction and alloreactivity. J Exp Med. 2002;195(5):571–81.PubMedGoogle Scholar
  130. 130.
    Reinherz EL, Tan K, Tang L, Kern P, Liu J, Xiong Y, et al. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science. 1999;286(5446):1913–21.PubMedGoogle Scholar
  131. 131.
    Hare BJ, Wyss DF, Osburne MS, Kern PS, Reinherz EL, Wagner G. Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor. Nat Struct Biol. 1999;6(6):574–81.PubMedGoogle Scholar
  132. 132.
    Maynard J, Petersson K, Wilson DH, Adams EJ, Blondelle SE, Boulanger MJ, et al. Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity. 2005;22(1):81–92.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyUniversity of North Carolina at Chapel HillChapel HillUSA

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