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αβ T-Cell Receptor Repertoires Among Cytotoxic and Helper T Lymphocytes

  • David M. Kranz
  • Benjamin Tjoa

Abstract

It has become clear, since the discovery of the genes that encode the a chain and the β chain of the T-cell receptor (TCR), that the potential repertoire of receptors that could be generated is quite large ( ~ 1018 by one estimate). Previous reviews have described the genetic mechanisms that generate such diversity (Kronenberg et al., 1986; Davis and Bjorkman, 1988). The mechanisms include the assorted use of different variable (V) region genes ( ~ 30Vβ and ~ 100Vα), diversity (D) gene segments (2 Dβ), and joining (J) gene segments (12 Jβ and ~ 50 Jα). Even greater diversity is generated in the CDR3 equivalent of immunoglobulins through the use of three mechanisms that operate at the junctions of the rearranged genes (i.e., VβDβ, DβJβ, and VαJα). These mechanisms involve the template-independent addition of nucleotides by the enzyme terminal deoxynucleotidyl transferase, the variable deletion of bases from the coding ends of genes, and the use of palindromic nucleotides at the ends of full-length gene segments (Lafaille et al., 1989).

Keywords

Major Histocompatibility Complex Gene Segment Major Histocompatibility Complex Molecule Mixed Lymphocyte Reaction Reticulum Cell Sarcoma 
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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References

  1. Aebischer TS, Oehen S, Hengartner H (1990): Preferential usage of Vα4 and Vβ10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein-specific H-2Db-restricted cytotoxic T cells. Eur J Immunol 20: 523–531CrossRefGoogle Scholar
  2. Ajitkumar P, Geier SS, Kesari KV, Borriello F, Nakagawa M, Bluestone JA, Saper MA, Wiley DC, Nathenson SG (1988): Evidence that multiple residues on both the a-helices of the class I MHC molecule are simultaneously recognized by the T cell receptor. Cell 54: 47–56CrossRefGoogle Scholar
  3. Beall SS, Lawrence JV, Bradley DA, Mattson DH, Singer DS, Biddison WE (1987): β-chain gene rearrangements and Vβ gene usage in DPw2-specific T cells. J Immunol 139: 1320–1325Google Scholar
  4. Berg LJ, Pullen AM, Fazekas de St Groth B, 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: 1035–1046CrossRefGoogle Scholar
  5. Bill J, Kanagawa O. Woodland DL. Palmer E (1989a): The MHC molecule I-E is necessary but not sufficient for the clonal deletion of Vß-bearing T cells. J Exp Med 169: 1405–1419CrossRefGoogle Scholar
  6. Bill J, Yague J, Appel VB, White J, Horn G, Erlich HA. Palmer E (1989b): Molecular genetic analysis of 1781-AO’ reactive T cells. J Exp Med 169: 115–133CrossRefGoogle Scholar
  7. Blackman M, Kappler J, Marrack P (1990): The role of the T cell receptor in positive and negative selection of developing T cells. Science 248: 1335–1341CrossRefGoogle Scholar
  8. Borst J, De Vries E, Spits H, De Vries JE, Boylston AW, Matthews EA (1987): Complexity of T cell receptor recognition sites for defined alloantigens. J Immunol 139: 1952–1959Google Scholar
  9. Chen L-K, Mathieu-Mahul D, Bach FH, Dausset J, Bensussan A, Sasportes M (1986): Recombinant interferon a can induce rearrangement of T-cell antigen receptor a-chain genes and maturation to cytotoxicity in T-lymphocyte clones in vitro. Proc Natl Acad Sci USA 83: 4887–4889CrossRefGoogle Scholar
  10. Danska JS, Livingstone AM, Paragas V, Ishihara T, Fathman CG (1990): The presumptive CDR3 regions of both T cell receptor α and β chains determine T cell specificity for myoglobin peptides. J Exp Med 172: 27–33CrossRefGoogle Scholar
  11. Davis MM, Bjorkman PJ (1988): T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402CrossRefGoogle Scholar
  12. Engel I, Hedrick SM (1988): Site-directed mutations in the VDJ junctional region of α T cell receptor β chain causes changes in antigenic peptide recognition. Cell 54: 473–484CrossRefGoogle Scholar
  13. Epplen JT, Bartels F, Becker A, Nerz G, Prester M, Rinaldy A, Simon MM (1986): Change in antigen specificity of cytotoxic T lymphocytes is associated with the rearrangement and expression of a T-cell receptor β-chain gene. Proc Natl Acad Sci USA 83: 4441–4445CrossRefGoogle Scholar
  14. Falcioni G, Dembic A, Muller S, Lehmann PV, Nagy ZA (1990): Flexibility of the T cell repertoire: Self tolerance causes a shift of T cell receptor gene usage in response to insulin. J Exp Med 171: 1665–1681CrossRefGoogle Scholar
  15. Fink PJ, Blair MJ, Matis LA, Hedrick SM (1990): Molecular analysis of the influences of positive selection, tolerance induction, and antigen presentation on the T cell receptor repertoire. J Exp Med 172: 139–150CrossRefGoogle Scholar
  16. Fink PJ, Matis LA, McElligott DL, Bookman MA, Hedrick SM (1986): Correlations between T cell specificity and the structure of the antigen receptor. Nature 321: 219–226CrossRefGoogle Scholar
  17. Fry AM, Matis LA (1988): Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature 335: 830–832CrossRefGoogle Scholar
  18. Gajewski TF, Schell SR, Nau G, Fitch FW (1989): Regulation of T-cell activation: Differences among T-cell subsets. Immunol Rev 111: 79–110CrossRefGoogle Scholar
  19. Garman R, Ko J-L, Vulpe C, Raulet D (1986): T-cell receptor variable gene usage in T-cell populations. Proc Natl Acad Sci USA 83: 3987–3991CrossRefGoogle Scholar
  20. Gregoire C, Rebai N, Schweisguth F, Necker A, Mazza G, Auphan N, Millward A, Schmitt-Verhulst A-M, Malissen B (1991): Engineered secreted T-cell receptor heterodimers. Proc Nal Acad Sci USA 88: 8077–8081CrossRefGoogle Scholar
  21. Haskins K, Hannum C, White J, Toehm N, Kubo R, Kappler J, Marrack P (1984): The antigen-specific major histocompatibility complex restricted receptor on T cells VI. An antibody to a receptor allotype. J Exp Med 160: 452–471CrossRefGoogle Scholar
  22. Hedrick SM. Engel I, McElligott DL, Fink PJ, Hsu M, Hansburg D, Matis LA (1988): Selection based on specificity for amino acid sequences in the putative third hypervariable region of the beta chain of the T cell antigen receptor. Science 239: 1541–1544CrossRefGoogle Scholar
  23. Hirama T, Takeshita S, Matsubayashi Y, Iwashiro M, Masuda T, Kuribayashi K, Yoshida Y, Yamagishi H (1991): Conserved V(D)J junctional sequence of cross-reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution. Eur J Immunol 21: 483–488CrossRefGoogle Scholar
  24. Hochgeschwender E, Welzien H, Eichmann K, Wallace R, Epplen J (1986): Preferential expression of a defined T-cell receptor β-chain gene in hapten-specific cytotoxic T-cell clones. Nature 322: 376–378CrossRefGoogle Scholar
  25. Hochgeschwender U, Simon H-G, Weltzien HU, Bartels F, Becker A, Epplen JT (1987): Dominance of one T-cell receptor in the H-2 Kb/TNP response. Nature 326: 307–309CrossRefGoogle Scholar
  26. Iwamoto A, Ohashi PS, Pircher H, Walker CL, Michalopoulos EE, Rupp F, Hengartner H, Mak TW (1987): T cell receptor variable gene usage in a specific cytotoxic T cell response: Primary structure of the antigen-MHC receptor of four haptet-specific cytotoxic T cell clones. J Exp Med 165: 591–600CrossRefGoogle Scholar
  27. Jameson SC, Kaye J, Gascoigne NRJ (1990): A T cell receptor Va region selectively expressed in CD4+ cells. J Immunol 145: 1324–1331Google Scholar
  28. Jameson SC, Nakajima PB, Brooks JL, Heath W, Kanagawa O, Gascoigne NRJ (1991): The T cell receptor Val 1 gene family: Analysis of allelic sequence polymorphism and demonstration of Ja region-dependent recognition by allele-specific antibodies. J Immunol 147: 3185–3193Google Scholar
  29. Kanagawa O, Palmer E, Bill J (1989): The T cell receptor Vß6 domain imparts reactivity to the Mls-l’ antigen. Cell Immunol 119: 412–426CrossRefGoogle Scholar
  30. Kappler JW, Wade T, White J, Kushnir E, Blackman M, Bill J, Roehm N, Marrack P (1987): A T cell receptor Vß segment that imparts reactivity to a class II major histocompatibility complex product. Cell 49: 263–271CrossRefGoogle Scholar
  31. Katz JD, Ohnishi K, Lebow LT, Bonavida B (1989): The SJL/J T cell response to both spontaneous and transplantable syngeneic reticulum cell sarcoma is mediated predominantly by the Vβl7a+ T cell clonotype. J Exp Med 168: 1553–1562CrossRefGoogle Scholar
  32. Kisielow P, Teh HS, Bluthmann H, von-Boehmer (1988): Positive selection of antigen-specific T cells in thymus by restrictig MHC molecules. Nature 335: 730–733CrossRefGoogle Scholar
  33. Kronenberg M, Siu G, Hood LE, Shastri N (1986): The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Ann Rev Immunol 4: 529–591CrossRefGoogle Scholar
  34. Lafaille JJ, DeCloux A, Bonneville M, Takagaki Y, Tonegawa S (1989): Junctional sequences of T cell receptor yd genes: implications for γδ T cell lineages and for a novel intermediate of V-(D)-J joining. Cell 59: 859–870CrossRefGoogle Scholar
  35. Liao N, Maltzman J, Raulet DH (1989): Positive selection determines T cell receptor Vß14 gene usage by CD8+ cells. J Exp Med 170: 135–143CrossRefGoogle Scholar
  36. MacDonald HR, Glasebrook AL, Bron C, Kelso A, Cerottini J-C (1982): Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on CTL: Possible implications for the affinity of CTL antigen receptors. Immunol Rev 68: 69–85CrossRefGoogle Scholar
  37. Malissen M, Trucy J, Letourneur F, Rebai N, Dunn DE, Fitch FW, Hood L, Malissen B (1988): A T cell clone expresses two T cell receptor a genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition. Cell 55: 49–59CrossRefGoogle Scholar
  38. Marolleau JP, Fondell JD, Malissen M, Trucy J, Barbier E, Marcu KB, Cazenave DA, Primi D (1988): The joining of germ-line Va to Ja genes replaces the preexisting VaJa complexes in a T cell receptor αβ positive T cell line. Cell 55: 291–300CrossRefGoogle Scholar
  39. Marrack P, Kappler J (1990): The staphylococcal enterotoxins and their relatives. Science 248: 705–711CrossRefGoogle Scholar
  40. Miceli MC, Finn OJ (1989): T cell receptor ß-chain selection in human allograft rejection. Jlmmunol 142: 81–86Google Scholar
  41. Morel PA, Livingstone AM, Fathman CG (1987): Correlation of T cell receptor Vβ gene family with MHC restriction. J Exp Med 166: 583–588CrossRefGoogle Scholar
  42. Moss PAH, Moots RJ, Rosenberg WMC, Rowland-Jones SJ, Bodmer HC, McMichael AJ, Bell JI (1991): Extensive conservation of α and β chains of the human T-cell antigen receptor recognizing HLA-A2 and influenza A matrix peptide. Proc Natl Acad Sci USA 88: 8987–8991CrossRefGoogle Scholar
  43. Necker AN, Rebai N, Matthes M, Jouvin-Marche E, Cazenave P, Swarnworawong P, Palmer E, MacDonald HR, Malissen B (1991): Monoclonal antibodies raised against engineered soluble mouse T cell receptors and specific for Vα8-, Vβ2- or Vβ10-bearing T cells. Eur J Immunol 21: 3035–3040CrossRefGoogle Scholar
  44. Nitta T, Oksenberg JR, Rao NA, Steinman L (1990): Predominant expression of T cell receptor Vα7 in tumor-infiltrating lymphocytes of uveal melanoma. Science 249: 672–674CrossRefGoogle Scholar
  45. Okada CY, Horlzmann B, Guidos C, Palmer E, Weissman IL (1990): Characterization of a rat monoclonal antibody specific for a determinant encoded by the Vβ7 gene segment: Depletion of Vβ7+ T cells in mice with Mls-l’ haplotype. Jlmmunol 144: 3473–3477.Google Scholar
  46. Payne J, Huber BT, Cannon NA, Schneider R, Schilham MW, Acha-Orbea H, MacDonald HR, Hengartner H (1988): Two monoclonal rat antibodies with specificity for the β-chain variable region Vβ6 of the murine T-cell receptor. Proc Natl Acad Sci USA 85: 7695–7698CrossRefGoogle Scholar
  47. Pircher H, Moskophidis D, Rohrer U, Burki K, Hengartner H, Zinkernagel RM (1990): Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature 346: 629–633CrossRefGoogle Scholar
  48. Pullen AM, Marrack P, Kappler JW (1988): The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature 335: 796–801CrossRefGoogle Scholar
  49. Reich EP, Sherwin RS, Kanagawa O, Janeway CA, Jr (1989): An explanation for the protective effect of the MHC class II I-E molecule in murine diabetes. Nature 341: 326–328CrossRefGoogle Scholar
  50. Reimann J, Bellan A (1986): Use of Vß8 genes in splenic Lyt-2+ cytotoxic lymphocyte precursors reactive to bm1 or bm14 alloantigen in individual C57BL/6 mice. Eur J Immunol 16: 1597–1602CrossRefGoogle Scholar
  51. Rodewald HR, Koszinowski UH, Eichmann K, Melchers I (1989): Predominant utilization of Vβ8 T cell receptor genes in the H-2Ld-restricted cytotoxic T cell response against the immediate-early protein pp89 of the murine cytomegalovirus. J Immunol 143: 4238–4243Google Scholar
  52. Roth ME, Holman PO, Kranz DM (1991): Non-random use of Ja gene segments: Influence of Vα and Jα gene location. J Immunol 147: 1075–1081Google Scholar
  53. Saito T, Germain RN (1989): Marked differences in the efficiency of expression of distinct αβ T cell receptor heterodimers. J Immunol 143: 3379–3384Google Scholar
  54. Schilham MW, Lang R, Acha-Orbea H, Benner R, Joho R, Hengartner H (1987): Fine specificity and T cell receptor β-chain rearrangements of five H-2D6-specific cytotoxic T-cell clones. Immunogenetics 25: 171–178CrossRefGoogle Scholar
  55. Sha WC, Nelson CA, Newbury RD, Kranz DM, Russell JH, Loh DY (1988): Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 335: 271–274CrossRefGoogle Scholar
  56. Sherman DH, Hochman PS, Dick R, Tizard R, Ramachandran KL, Flavell RA, Huber BT (1987): Molecular analysis of antigen recognition by insulin-specific T-cell hybridomas from B6 wild-type and bm12 mutant mice. Mol Cell Biol 7: 1865–1872Google Scholar
  57. Spinella DG, Hansen TH, Walsh WD, Behlke MA, Tillinghast JP, Chou HS, Whiteley PJ, Kapp JA, Pierce CW, Shevach EM, Loh DY (1987): Receptor diversity of insulin-specific T cell lines from C57BL (H-2h) mice. J Immunol 138: 3991–3995Google Scholar
  58. Staerz UD, Rammensee HG, Benedetto JD, Bevan MJ (1985): Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol 134: 3994–4000Google Scholar
  59. Tan K-N, Datlof BM, Gilmore JA, Kroman AC, Lee JH, Maxam AM, Rao A (1988): The T cell receptor Vα3 gene segment is associated with reactivity to p-azobenzenearsonate. Cell 54: 247–261CrossRefGoogle Scholar
  60. Taylor AH, Haberman AM, Gerhard W, Caton AJ (1990): Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin. J Exp Med 172: 1643–1651CrossRefGoogle Scholar
  61. Tjoa B, Kranz DM (1992): Diversity of T cell receptor-a chain transcripts from hyperimmune alloreactive T cells. J Immunol 149: 253–259Google Scholar
  62. Tomonari K, Lovering E (1988): T-cell receptor-specific monoclonal antibodies against a Vβ-positive mouse T-cell clone. Immunogenetics 28: 445–451CrossRefGoogle Scholar
  63. Tomonari K, Lovering E, Fairchild S, Spencer S (1989): Two monoclonal antibodies specific for the T cell receptor Vα8. Eur J Immunol 19: 1131–1135CrossRefGoogle Scholar
  64. Tomonari K, Lovering E, Spencer S (1990): Correlation between the Vβ4+CD8’ T-cell population and the H-2d haplotype. Immunogenetics 31: 333–339CrossRefGoogle Scholar
  65. Utsunomiya TJ, Bill J, Palmer E, Gollob K, Takagaki Y, Kanagawa O (1989): Analysis of a monoclonal rat antibody directed to the a-chain variable region (Vα3) of the mouse T cell antigen receptor. J Immunol 143: 2602–2608Google Scholar
  66. Utsonomiya Y, Kosaka H, Kanagawa O (1991): Differential reactivity of Vβ9 T cells to minor lymphocyte stimulating antigen in vitro and in vivo. Eur J Immunol 21: 1007–1011CrossRefGoogle Scholar
  67. Vitetta ES, Berton MT, Burger, C, Kepron M, Lee WT, Yin X-M (1991): Memory B and T-cells. Ann Rev Immunol 9: 193CrossRefGoogle Scholar
  68. Winoto A, Urban JL, Lan NC, Goverman J, Hood L, Hansburg D (1986): Predominant use of a Vα gene segment in mouse T-cell receptors for cytochrome c. Nature 324: 679–682CrossRefGoogle Scholar
  69. Wither J, Pawling J, Phillips L, Delovitch T, Hozumi N (1991): Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas. J Immunol 146: 3513–3522Google Scholar
  70. Yanagi Y, Maekawa R, Cook T, Kanagawa O, Oldstone MB (1990): Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus. J Virol 64: 5919–5926Google Scholar
  71. Zaller DM, Osman G, Kanagawa O, Hood L (1990): Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor Vβ-specific antibodies. J Exp Med 171: 1943–1955.CrossRefGoogle Scholar

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© Birkhäuser Boston 1993

Authors and Affiliations

  • David M. Kranz
  • Benjamin Tjoa

There are no affiliations available

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