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T-cell receptors in immune responses

  • M. A. Robinson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 386)

Abstract

T lymphocytes play a central role in the generation of both humoral and cell-mediated immune responses. Although T-cells mediate diverse effector functions, most recognize antigenic peptide presented by molecules encoded within the major histocompatibility complex (MHC). The fine specificity of a T-cell is determined by a heterodimeric receptor for antigen (TCR) displayed on the cell surface. The TCR present on the majority of T-cells is composed of an alpha and a beta chain which are similar to immunoglobulins (Ig) in both sequence and gene organization. Genes for the alpha and beta chains of the TCR are encoded in germline DNA as discontinuous gene segments that rearrange specifically in T-cells during development. The variable regions of each of these chains are responsible for antigen recognition and are encoded by juxtaposed variable (V), diversity (D) (for beta chains), and joining (J) gene segments (reviewed in Toyonaga and Mak, 1987; Wilson et al., 1988; Davis and Bjorkman, 1988). A critical difference between TCR and Ig is that somatic mutation does not appear to play a role in the generation of TCR diversity (Ikuta et al., 1985), which emphasizes the importance of germline polymorphism of TCR gene segments. Knowledge of both the extent and variability of the germline TCR repertoire is critical to understanding the diversity of potential T-cell specificities.

Keywords

Major Histocompatibility Complex Gene Segment Major Histocompatibility Complex Gene Beta Chain Major Histocompatibility Complex Antigen 
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. Baccala, R., Kono, D.H., Walker, S., Balderas, R.S., and Theofilopoulos, A.N.: Genomically imposed and somatically modified human thymocyte Vß gene repertoires. Proc Natl Acad Sci USA88: 2908–2912, 1991PubMedCrossRefGoogle Scholar
  2. Baccala, R., Kono, D.H., Walker, S., Balderas, R.S., and Theofilopoulos, A.N.: Genomically imposed and somatically modified human thymocyte Vß gene repertoires. Proc Natl Acad Sci USA88. 2908–2912, 1991PubMedCrossRefGoogle Scholar
  3. Beall, S.S., Concannon, R, Charmley, R, McFarland, H.R, Gatti, R.A., Hood, L.E., McFarlin, D.E. and Biddison, W.E.: The germline repertoire of T-cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis. J Neuroimmunol21: 59–66, 1989PubMedCrossRefGoogle Scholar
  4. Borden, P, Jaenichen, R., and Zachau, H.G.: Structural features of transposed human VK genes and implications for the mechanism of their transpositions. Nucleic Acids Res18. 2101–2107, 1990PubMedCrossRefGoogle Scholar
  5. Cazenave, P-A., Marche, P., Jouvin-Marche, E., Voegtle, D., Bonhomme, F., Bandeira, A. and Coutinho, A.: Vßl7-gene polymorphism in wild-derived mouse strains: Two amino acid substitutions in the Vß 17 region alter drastically T-cell receptor specificity. Cell 63:717Google Scholar
  6. Charmley, P., Wang, K., Hood, L., and Nickerson, D.A.: Identification and physical mapping of a polymorphic human T-cell receptor V beta gene with a frequent null allele. J. Exp Med77: 135–143, 1993aCrossRefGoogle Scholar
  7. Charmley, P., Wei, S., and Concannon, P.: Polymorphisms in the Tcrß-V2 gene segments localize the Tcrb orphon genes to human chromosome 9p21. Immunogenetics38.283– 186, 1993bGoogle Scholar
  8. Chothia, C, Boswell, D.R. and Lesk, R.M.: The outline structure of the T-cell alpha beta receptor. EMBOJ: 3745–3755, 1988Google Scholar
  9. Concannon, P., Gatti, R.A. and Hood, L.E.: Human T-cell receptor Vß gene polymorphism. J. Exp. Med.165: 1130–1140, 1987PubMedCrossRefGoogle Scholar
  10. Concannon, P., Pickering, L.A., Kung, P. and Hood, L.: Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci USA83, 6598–6602, 1986PubMedCrossRefGoogle Scholar
  11. Cornelis, F., Pile, K., Loveridge, J., Moss, P., Harding, R., Julier, C.,and Bell, J.: Systematic study of human alpha beta T-cell receptor V segments shows allelic variations resulting in a large number of distinct T-cell receptor haplotypes. Eur J Immunol. 23: 1277–1283, 1993PubMedCrossRefGoogle Scholar
  12. Davis, M.M. and Bjorkman, PJ.: T-cell antigen receptor genes and T-cell recognition, Nature334: 395–402, 1988PubMedCrossRefGoogle Scholar
  13. Day, C.E., Zhao, T. and Robinson, M.A.: Silent allelic variants of a T-cell receptor Vß12 gene are present in diverse human populations. Hum Immunol34: 196–202, 1992PubMedCrossRefGoogle Scholar
  14. Diaz, M.O., Ziemin, S., Le Beau, M.M., Pitha, P., Smith, S.D., Chilcote, R.R., Rowley, J.D.: Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines. Proc Natl Acad Sci USA85: 5259–5263, 1988PubMedCrossRefGoogle Scholar
  15. Gahm, S-J., Fowlkes, B.J., Jameson, S.D., Gascoigne, N.RJ., Cotterman, M.M., Kanagawa, O., Schwartz, R.H., and Matis, L.A.: Profound alteration in an aß T-cell antigen receptor repertoire due to polymorphism in the first complementarity-determining region of the ß chain. Proc Natl Acad Sd.USA, 88: 10267–10271, 1991CrossRefGoogle Scholar
  16. Hansen, T., Ronningen, K.S., Ploski, R., Kimura, A., and Thorsby, E.: Coding region polymorphisms of human T-cell receptor V beta 6.9 and V beta 21.4. Scand J Immunol36: 285–290, 1992PubMedCrossRefGoogle Scholar
  17. Huber, C, Thiebe, R., Hameister, H., Smola, H., Lötscher, E. and Zachau, H.G.: A human immunoglobulin kappa orphon without sequence defects may be the product of a pericentric inversion. Nucleic Acids Res18. 3475–3478, 1990PubMedCrossRefGoogle Scholar
  18. Ikuta, K., Ogura, T, Shirnizu, A. and Honjo, T.: Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors. Proc Natl Acad Sci USA82. 7701–7705, 1985PubMedCrossRefGoogle Scholar
  19. Isobe, M., Erikson, J., Emanuel, B., Nowell, P., and Croce, C: Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells. Science228. 580–583, 1985PubMedCrossRefGoogle Scholar
  20. Li, Y., Szabo, P., Robinson, M.A., Dong, B., Posnett, D.N.: Allelic variations in the human T-cell receptor V beta 6.7 gene products. J Exp Med171: 221–230, 1990PubMedCrossRefGoogle Scholar
  21. Luyrink, L., Gabriel, C.A., Thompson, S.D., Grom, A.A., Maksymowych, W.P., Choi, E., and Glass, D.: Reduced expression of a human Vß6.1 T-cell receptor allele. Proc Natl Acad Sci USA90. 4369–4373, 1993PubMedCrossRefGoogle Scholar
  22. Matsuda, R, Shin, E.K., Hirabayashi, Y., Nagaoka, H., Yoshida, M.C., Zong, S.Q. and Honjo, T.: Organization of variable region segments of the human immunoglobulin heavy chain: Duplication of the D5 cluster within the locus and interchromosomal translocation of variable region segments. EMBOJ 9. 2501–2506, 1990Google Scholar
  23. Nanda, N.K., Apple, R., and Sercarz, E.: Limitations in plasticity of the T-cell receptor repertoire, Proc Natt Acad Sci USA88: 9503–9507, 1991CrossRefGoogle Scholar
  24. Nepom, G.T. and Concannon, P.: Molecular genetics of autoimmunity. In: Rose, N.R., and Mackay I.R. (eds). The Autoimmune Diseases. Academic Press, Inc., N.Y. pp. 127–152, 1992Google Scholar
  25. Padovan, E., Casorati, G., Dellabona, P., Meyer, S., Brockhaus, M., and Lanzavecchia, A., Expression of two T-cell receptor χ chains: Dual receptor T-cells. Science262: 422–424, 1993PubMedCrossRefGoogle Scholar
  26. Plaza, A., Kono, D.H. and Theofilopoulos, A.N.: New human Vß genes and polymorphic variants. J Immunol147: 4360–4365, 1991PubMedGoogle Scholar
  27. Posnett, D.N., Gottlieb, A., Bussel, J.B., Friedman, SM., Chiorazzi, N., Li, Y.r Szabo, P., Farid, N.R., Robinson, M.A.: T-cell antigen receptors in autoimmunity. J Immunol141: 1963–1969, 1988PubMedGoogle Scholar
  28. Robinson, M.A.: Allelic sequence variations in the hypervariable region of a T-cell receptor ß chain: Correlation with restriction fragment length polymorphism in human families and populations. Proc Natl Acad Sci USA86: 9422–9426, 1989PubMedCrossRefGoogle Scholar
  29. Robinson, M.A.: The human T-cell receptor beta-chain gene complex contains at least 57 variable gene segments: Identification of six Vbeta genes in four new families. J. Immunol146, 4392–439, 1991PubMedGoogle Scholar
  30. Robinson, MA.: Usage of human T-cell receptor Vß, Jß, Cß, and Vα gene segments is not proportional to gene number. Hum Immunol. 35: 60–67, 1992PubMedCrossRefGoogle Scholar
  31. Robinson, M.A., and Kindt, T.J.: linkage between T-cell receptor genes and susceptibility to multiple sclerosis: A complex issue. Regional Immunol4: 274–283, 1992Google Scholar
  32. Robinson, M.A., Mitchell, M.P., Wei, S., Day, C.E., Zhao, T.M., Concannon, P.: Organization of human T-cell receptor beta-chain genes: Clusters of V beta genes are present on chromosomes 7 and 9. Proc Natl Acad Sci USA90. 2433–2437, 1993PubMedCrossRefGoogle Scholar
  33. Schaeffer, E.B., Sette, A., Johnson, D.L., Bekoff, M.C., Smith, J.A., Grey, H.M., and Buus, S. Relative contribution of “determinant selection” and “holes in the T-cell repertoire” to T-cell responses. Proc Natl Acad Sci USA86: 4649–4653, 1989PubMedCrossRefGoogle Scholar
  34. Seboun, E., Robinson, M.A., Doolittle, T.H., Ciulla, T.A., Kindt, TJ., and Hauser, S. L.: A susceptibility locus for multiple sclerosis is linked to the T-cell receptor beta chain complex. Cell57: 1095–1100, 1989aCrossRefGoogle Scholar
  35. Seboun, E., Robinson, M.A., Kindt, TJ. and Hauser, S.L.: Insertion/deletion-related polymorphisms in the human T-cell receptor beta gene complex. J Exp Med170. 1263–1270, 1989bCrossRefGoogle Scholar
  36. Toyonaga, B. and Mak, T.W.: Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol5: 585–620, 1987PubMedCrossRefGoogle Scholar
  37. Wilson, R.K., Lai, E., Concannon, P., Barth, R.K. and Hood, L.E.: Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev101: 149–204. 1988PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1995

Authors and Affiliations

  • M. A. Robinson
    • 1
  1. 1.Laboratory of Immunogenetics, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleUSA

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