Advertisement

Diversity, Development, Ligands, and Probable Functions of γδ T Cells

  • Susumu Tonegawa
  • Anton Berns
  • Marc Bonneville
  • Andrew G. Farr
  • Isao Ishida
  • Kouich Ito
  • Shigeyoshi Itohara
  • Charles A. JanewayJr.
  • Osami Kanagawa
  • Ralph Kubo
  • Juan J. Lafaille
  • Donal B. Murphy
  • Nobuki Nakanishi
  • Yohtaro Takagaki
  • Sjek Veebeek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 292)

Abstract

The most critical step in the vertebrate immune response is the recognition of antigens by lymphocytes. This task is accomplished by two sets of glycoproteins, immunoglobulins and T cell antigen-receptors (TCRs). The most extraordinary feature of these proteins is their structural variability, much of which originates from the ability of the encoding gene segments to undergo somatic rearrangement.1 All TCRs were initially thought to be composed of a heterodimeric protein composed of α and β subunits. However, the search for the genes encoding these polypeptides led to the identification of a third rearranging gene2,3 which was later shown to code for one of the two subunits of another heterodimeric, TCR γδ.4–6

Keywords

Peripheral Lymphoid Organ Somatic Rearrangement Junctional Diversity Adult Thymus Intestinal Intraepithelial Lymphocyte 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    S. Tonegawa, Somatic generation of antibody diversity, Nature 302:575 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    H. Saito, D. M. Kranz, Y. Takagaki, A. C. Hayday, H. N. Eisen, and S. Tonegawa, Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences, Nature 309:757 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    A. C. Hayday, H. Saito, S. D. Gillies, D. M. Kranz, G. Tanigawa, H. N. Eisen, and S. Tonegawa, Structure organisation and somatic rearrangement of T cell “gamma genes”Cell 40:259 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    M. B. Brenner, J. McLean, D. P. Dialynas, J. L. Strominger, J. A. Smith, F. L. Owen, J. G. Seidman, S. Ip, F. Rosen, and M. S. Krangel, Identification of a putative second T-cell receptor, Nature 322: 145 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    I. Bank, R. A. DePinho, M. B. Brenner, J. Cassimeris, F. W. Alt, and L. Chess, A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes, Nature 322:179 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Weiss, M. Newton, and D. Crommie, Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer, Proc. Natl. Acad. Sci. USA 83:6998 (1986).PubMedCrossRefGoogle Scholar
  7. 7.
    A. M. Lew, D. M. Pardoll, W. L. Maloy, B. J. Fowlkes, A. Kruisbeek, S.-F. Cheng, R. N. Germain, J. A. Bluestone, R. H. Schwartz, and J. E. Coligan, Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes, Science 234: 1401 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    N. Nakanishi, K. Maeda, K. Ito, M. Heller, and S. Tonegawa, T protein is expressed on murine fetal thymocytes as a disulphide-linked heterodimer, Nature 325:720 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    K. Maeda, N. Nakanishi, B. L. Rogers, W. G. Haser, K. Shitara, H. Yoshida, Y. Takagaki, A. A. Augustin, and S. Tonegawa, Expression of T gene products on the surface of peripheral T cells and T cell blasts generated by allogeneic mixed lymphocyte reaction, Proc. Natl. Acad. Sci. USA 84:6536 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    G. Stingl, K. C. Gunter, E. Tschachler, H. Yamada, R. I. Lechler, W. M. Yokoyama, G. Steiner, R. N. Germain, and E. M. Shevach, Thyl+ dendritic epidermal cells belong to the T cell lineage, Proc. Natl. Acad. Sci. USA 84:2430 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    W. A. Kuziel, A. Takashima, M. Bonhadi, P. R. Bergstresser, J. P. Allison, R. E. Tigelaar, and P. W. Tucker, Regulation of T-cell receptor -chain RNA expression in murine Thy-1+ dendritic epidermal cells, Nature 328:263 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    M. Bonneville, C. A. Janeway, Jr., K. Ito, W. Haser, I. Ishida, N. Nakanishi, and S. Tonegawa, Intestinal intraepithelial lymphocytes are a distinct set ofT cells, Nature 336:479 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    T. Goodman and L. Lefrancois, Expression of theT-cell receptor on intestinal CD8+ intraepithelial lymphocytes, Nature 333:855 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Itohara, N. Nakanishi, O. Kanagawa, R. Kubo, and S. Tonegawa, Monoclonal antibodies specific to native murine T cell receptor : Analysis ofT cells in thymic ontogeny and peripheral lymphoid organs, Proc. Natl. Acad. Sci. USA 86:5094 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    R. P. Bucy, C.-L. H. Chen, J. Cihak, U. Löch, and M. D. Cooper, Avian T cells expressingreceptors localize in the splenic sinusoids and the intestinal epithelium, J. Immunol. 141:2200 (1988).PubMedGoogle Scholar
  16. 16.
    V. Groh, S. Porcelli, M. Fabbi, L. L. Lanier, L. J. Picker, T. Anderson, R. A. Warnke, A. K. Bhan, J. L. Strominger, and M. B. Brenner, Human lymphocytes bearing T cell receptorare phenotypically diverse and evenly distributed throughout the lymphoid system, J. Exp. Med. 169:1277 (1989).PubMedCrossRefGoogle Scholar
  17. 17.
    D. M. Asarnow, W. A. Kuziel, M. Bonyhadi, R. E. Tigelaar, P. W. Tucker, and J. P. Allison, Limited diversity ofantigen receptor genes of Thy-1+ dendritic epidermal cells, Cell 55:837 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    Y. Takagaki, A. DeCloux, M. Bonneville, and S. Tonegawa,T cell receptors on murine intestinal intra-epithelial lymphocytes are highly diverse, Nature 339:712 (1989).PubMedCrossRefGoogle Scholar
  19. 19.
    R. K. Saiki, D. H. Gelfand, S. Stoffel, S. J. Scharf, R. Higuchi, G. T. Horn, K. B. Mullis, and H. A. Erlich, Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase, Science 239:487 (1988).PubMedCrossRefGoogle Scholar
  20. 20.
    S. Itohara, A. G. Farr, J. J. Lafaille, M. Bonneville, Y. Takagaki, and S. Tonegawa, Athymocyte subset with homogenous T cell receptors homes to certain mucosal epithelia, Nature 343:754 (1989).CrossRefGoogle Scholar
  21. 21.
    W. L. Havran and J. P. Allison, Developmenta ordered appearance of thymocytes expressing different T-cell antigen receptors, Nature 335:443 (1988).PubMedCrossRefGoogle Scholar
  22. 22.
    K. Ito, M. Bonneville, Y. Takagaki, N. Nakanishi, O. Kanagawa, E. Krecko, and S. Tonegawa, Different T-cell receptors are expressed on thymocytes at different stages of development, Proc. Natl. Acad. Sci. USA 86:631 (1989).PubMedCrossRefGoogle Scholar
  23. 23.
    J. J. Lafaille, A. DeCloux, M. Bonneville, Y. Takagaki, and S. Tonegawa, Junctional sequences of T cell receptor γ and δ genes: Implications forT cell lineages and novel intermediates of V-(D)-J joinings, Cell 59:859 (1989).PubMedCrossRefGoogle Scholar
  24. 24.
    A. J. Korman, S. M. Galesic, D. Spencer, A. M. Kruisbeek, and D. Raulet, Predominant variable region gene usage by γ/δ T cell receptor-bearing cells in the adult thymus, J. Exp. Med. 168:1021 (1988).PubMedCrossRefGoogle Scholar
  25. 25.
    Y. Takagaki, N. Nakanishi, I. Ishida, O. Kanagawa, and S. Tonegawa, T cell receptor γ and δ genes preferentially utilized by adult thymocytes for the surface expression, J. Immunol. 142:2112 (1989).PubMedGoogle Scholar
  26. 26.
    M. J. Lacy, L. K. McNeil, M. E. Roth, and D. M. Kranz, T-cell receptor -chain diversity in peripheral lymphocytes, Proc. Natl. Acad. Sci. USA 86:1023 (1989).PubMedCrossRefGoogle Scholar
  27. 27.
    J. D. Ashwell, P. E. Cunningham, P. D. Noguchi, and D. Hernandez, Cell growth cycle block of T cell hybridomas upon activation with antigen, J. Exp. Med. 165:173 (1987).PubMedCrossRefGoogle Scholar
  28. 28.
    M. Bonneville, K. Ito, E. G. Krecko, S. Itohara, D. Kappes, I. Ishida, O. Kanagawa, C. A. Janeway, Jr., D. B. Murphy, and S. Tonegawa, Recognition of a self MHC TL region product by γδ T cell receptors, Proc. Natl. Acad. Sci. USA 86:5928 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    J. W. Kappler, N. Roehm, and P. Marrack, T cell tolerance by clonal elimination in the thymus, Cell 49:273 (1987).PubMedCrossRefGoogle Scholar
  30. 30.
    P. Kisielow, H. Bluthmann, U. D. Staerz, M. Steinmetz, and H. von Boehmer, Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes, Nature 333:742 (1988).Google Scholar
  31. 31.
    H. R. MacDonald, R. Schneider, R. K. Lees, R. C. Howe, H. Acha-Orbea, H. Festenstein, R. M. Zinkernagel, and H. Hengartner, T cell receptor Vuse predicts reactivity and tolerance to MLsa-encoded antigens, Nature 323:40 (1988).CrossRefGoogle Scholar
  32. 32.
    I. Ishida, S. Verbeek, M. Bonneville, A. Berns, and S. Tonegawa, T cell receptortransgenic mice suggest a role of a 7 gene silencer in the generation of / T cells, Proc. Natl. Acad. Sci. USA 87:3067–3071 (1990).PubMedCrossRefGoogle Scholar
  33. 33.
    J. A. Bluestone, R. Q. Cron, M. Cotteman, B. A. Houlden, and L. A. Matis, Structure and specificity of TCR on major histocompatibility complex antigen specific CD3+, CD4-, CD8-T lymphocytes, J. Exp. Med. 168:1989 (1988).Google Scholar
  34. 34.
    L. A. Matis, R. Cron, and J. A. Bluestone, Major histocompatibility complex-linked specificity ofreceptor-bearing T lymphocytes, Nature 33:262 1987.CrossRefGoogle Scholar
  35. 35.
    J. Holoshitz, F. Koning, J. E. Coligan, J. deBruyn, and S. Strober, Isolation of CD4 CD8-mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid, Nature 339:226 (1989).PubMedCrossRefGoogle Scholar
  36. 36.
    E. M. Janis, S. H. E. Kaufmann, R. H. Schwartz, and D. M. Pardoll, Activation ofT cells in the primary immune response to Mycobacterium tuberculosis, Science 244:713 (1989).PubMedCrossRefGoogle Scholar
  37. 37.
    R. L. Modlin, C. Pirmez, F. M. Hofman, V. Torigian, K. Uyemura, T. H. Rea, B. R. Bloom, and M. B. Brenner, Lymphocytes bearing antigen-specificT-cell receptors accumulate in human infectious disease lesions, Nature 339:544 (1989).PubMedCrossRefGoogle Scholar
  38. 38.
    R. L. O’Brien, M. P. Happ, A. Dallas, E. Palmer, R. Kubo, and W. Born, Stimulation of a major subset of lymphocytes expressing T cell receptorby an antigen derived from Mycobacterium tuberculosis, Cell 57:667 (1989).PubMedCrossRefGoogle Scholar
  39. 39.
    C. A. Janeway, Jr., B. Jones, and A. Hayday, Specificity and function of T cells bearing 7/5 receptors, Immunol. Today 9:73 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Susumu Tonegawa
    • 1
  • Anton Berns
    • 2
  • Marc Bonneville
    • 1
  • Andrew G. Farr
    • 3
  • Isao Ishida
    • 1
  • Kouich Ito
    • 1
  • Shigeyoshi Itohara
    • 1
  • Charles A. JanewayJr.
    • 4
  • Osami Kanagawa
    • 5
  • Ralph Kubo
    • 6
  • Juan J. Lafaille
    • 1
  • Donal B. Murphy
    • 7
  • Nobuki Nakanishi
    • 1
  • Yohtaro Takagaki
    • 1
  • Sjek Veebeek
    • 2
  1. 1.Howard Hughes Medical Institute Center for Research, Department of BiologyMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.The Netherlands Cancer Institute, Division of Molecular Genetics and Department of ChemistryUniversity of AmsterdamThe Netherlands
  3. 3.Department of Biological StructureUniversity of WashingtonSeattleUSA
  4. 4.Howard Hughes Medical InstituteYale University Medical SchoolNew HavenUSA
  5. 5.Eli Lilly Research LaboratoriesLa JollaUSA
  6. 6.National Jewish Center of Immunology and Respiratory MedicineDenverUSA
  7. 7.The Wadsworth CenterNew York State Department of HealthAlbanyUSA

Personalised recommendations