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How Strict Is the MHC Restriction of T Cells?

  • Rolf M. Zinkernagel

Abstract

Thymus-derived lymphocytes (T cells) are generally specific for a self determinant (self-H) expressed on the target-cell surface and coded by the major histocompatibility gene complex (MHC) (reviewed in Paul and Benacerraf, 1977; Katz, 1977; Zinkernagel and Doherty, 1979). T cells that mediate nonlytic functions, such as T helper cells, proliferating T cells, and T cells involved in delayed-type hypersensitivity against contact allergens or intracellular bacteria, are specific for H-2I determinants, whereas lytic T cells are specific for H-2K or D structures. Specificities both for self-H and for any foreign antigen (X) are clonally expressed and highly specific. It is still unclear whether this dual specificity reflects T-cell expression of a single receptor for a neoantigenic determinant combining self-H complexed with X or T-cell expression of two independent receptor sites for self-H and for X.

Keywords

Restriction Specificity Major Histocompatibility Gene Complex Lymphocytic Choriomeningitis Virus Scripps Clinic Immune Spleen Cell 
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. Bennink, J.R., and Doherty, P.C., 1978, Different rules govern help for cytotoxic T cells and B cells, Nature (London) 276:829–831.CrossRefGoogle Scholar
  2. Bevan, M.J., and Fink, P.J., 1978, The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells, Immunol. Rev. 42:4–19.CrossRefGoogle Scholar
  3. Blanden, R.V., and Andrew, M.E., 1979, Primary anti-viral cytotoxic T cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type, J. Exp. Med. 149:535–538.PubMedCrossRefGoogle Scholar
  4. Blanden, R.V., Bowern, N.A., Pang, T.E., Gardner, I.D., and Parish, C.R., 1975, Effects of thymus-independent (B) cells and the H-2 gene complex on antiviral function of immune thymus derived (T) cells, Aust. J. Exp. Med. Sci. 53:187.CrossRefGoogle Scholar
  5. Cohn, M., and Epstein, R., 1978, T-cell inhibition of humoral responsiveness. II. Theory on the role of restrictive recognition in immune regulation, Cell. Immunol. 39:125–153.PubMedCrossRefGoogle Scholar
  6. Doherty, P.C., and Bennink, J.R., 1979, Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex, J. Exp. Med. 149:150–157.PubMedCrossRefGoogle Scholar
  7. Fink, P.J., and Bevan, M.J., 1978, H-2 antigens of the thymus determine lymphocyte specificity, J. Exp. Med. 148:766–775.PubMedCrossRefGoogle Scholar
  8. Kappler, J.W., and Marrack, P., 1978, The role of H-2 linked genes in helper T cell function. IV. Importance of T cell genotype and host environment in I-region and Ir gene expression, J. Exp. Med. 148:1510–1522.PubMedCrossRefGoogle Scholar
  9. Katz, D.H., 1977, Lymphocyte Differentiation, Recognition and Regulation, Academic Press, New York.Google Scholar
  10. Kindred, B., 1979, Nude mice in immunology, Prog. Allergy 26:137–238.PubMedGoogle Scholar
  11. Langman, R.E., 1978, The role of the major histocompatibility complex in immunity: A new concept in the functioning of a cell-mediated immune system, Rev. Physiol. Biochem. Pharmacol. 81:1.PubMedCrossRefGoogle Scholar
  12. Matzinger, P., and Mirkwood, G., 1978, In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type, J. Exp. Med. 148:84–92.PubMedCrossRefGoogle Scholar
  13. Miller, J.F.A.P., and Osoba, D., 1967, Current concepts in the immunological function of the thymus, Physiol. Rev. 47:437–520.PubMedGoogle Scholar
  14. Miller, J.F.A.P., Gamble, J., Mottram, P., and Smith, F.I., 1979, Influence of thymus genotype on acquisition of responsiveness in delayed-type hypersensitivity, Scand. J. Immunol. 9:29–38.PubMedCrossRefGoogle Scholar
  15. Mims, C.A., and Blanden, R.V., 1972, Antiviral action of immune lymphocytes in mice infected with lymphocytic choriomeningitis virus, Infect. Immunol. 6:695.Google Scholar
  16. Mullbacher, A., and Blanden, R.V., 1979, H-2 linked control of cytotoxic T cell responsiveness to alphavirus infection: Presence of H-2Dk during differentiation and stimulation converts stem cells of low responder genotype to T cells of responder phenotype, J. Exp. Med. 149:786–790.PubMedCrossRefGoogle Scholar
  17. Paul, W.E., and Benacerraf, B., 1977, Functional specificity of thymus-dependent lymphocytes, Science 195:1293.PubMedCrossRefGoogle Scholar
  18. Pulkkinen, A.J., and Pfau, C.J., 1970, Plaque size heterogeneity: A genetic trait of lymphocytic choriomeningitis virus, Appl. Microbiol. 20:123.PubMedGoogle Scholar
  19. Sprent, J., von Boehmer, H., and Nabholz, M., 1975, Association of immunity and tolerance to host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain, J. Exp. Med. 142:321.PubMedCrossRefGoogle Scholar
  20. von Boehmer, H., Haas, W., and Jerne, N.K., 1978, Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice, Proc. Natl. Acad. Sci. U.S.A. 75:2439–2442.CrossRefGoogle Scholar
  21. Waldman, H., Pope, H., Bettles, C., and Davies, A.J.S., 1979, The influence of thymus on the development of MHC restrictions exhibited by T-helper cells, Nature (London) 277:137–138.CrossRefGoogle Scholar
  22. Zinkernagel, R.M., 1978, Thymus and lymphohemopoietic cells: Their role in T cell maturation, in selection of T cells’ H-2-restriction-specificity and in H-2 linked Ir gene control, Immunol. Rev. 42:224–270.PubMedCrossRefGoogle Scholar
  23. Zinkernagel, R.M., and Althage, A., 1979, Search for suppression of T cells specific for the second nonhost H-2 haplotype in F1 → P irradiation bone marrow chimeras, J. Immunol. 122:1742–1749.PubMedGoogle Scholar
  24. Zinkernagel, R.M., and Doherty, P.C., 1979, MHC-restricted cytotoxic T cells: Studies on the biological role of polymorphic major transplantation antigens determining T cell restriction-specificity function and responsiveness, Adv. Immunol. 27:52–142.Google Scholar
  25. Zinkernagel, R.M., and Welsh, R.M., 1976, H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D, J. Immunol. 117:1495–1502.PubMedGoogle Scholar
  26. Zinkernagel, R.M., Callahan, G.N., Althage, A., Cooper, S., Klein, P.A., and Klein, J., 1978a, On the thymus in the differentiation of “H-2 self-recognition” by T cells: Evidence for dual recognition?, J. Exp. Med. 147:882.PubMedCrossRefGoogle Scholar
  27. Zinkernagel, R.M., Althage, A., Cooper, S., Callahan, G., and Klein, J., 1978b, In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells, J. Exp. Med. 148:805.PubMedCrossRefGoogle Scholar
  28. Zinkernagel, R.M., Althage, A., and Callahan, G., 1979, Thymic reconstitution of nude F1 mice with one or both parental thymus grafts, J. Exp. Med. 150:693–697.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1981

Authors and Affiliations

  • Rolf M. Zinkernagel
    • 1
  1. 1.Department of ImmunopathologyScripps Clinic and Research FoundationLa JollaUSA

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