Biological Significance of the MHC

  • R. R. P. de Vries
Part of the Current Topics in Veterinary Medicine and Animal Science book series (CTVM, volume 52)

Abstract

In this review the biological significance of the MHC is discussed. The author confines himself to class I and II genes and their products. Class I and II molecules present processed antigens to T cells. This function is operative during the development of a self-tolerant T cell repertoire and during an ongoing immune response. Both MHC class I and II genes are extremely polymorphic. This polymorphism results in inter-individual differences in immune reactivity. Therefore these genes are so-called Immune response (Ir-) genes. The resulting differences in immune reactivity are due to differential binding of processed antigen to the products of these Ir-genes. The MHC polymorphism has been conserved in evolution and there is evidence that selection by infectious disease has been involved in this process. An explanation for this is presented, which amounts to the idea that MHC polymorphism is a very pragmatic answer to the unpredictable challenges of infectious diseases. One of the consequences of this type of life-insurance is that individuals with certain MHC alleles have an increased susceptibility to certain immuno-pathological diseases. These recent developments in immunogenetics may be applied to the development of sub-unit vaccines, have implications for the prevention of T cell mediated immunopathological diseases and may result in genetic manipulation aimed at introducing resistance genes in susceptible animals.

Keywords

Major Histocompatibility Complex Major Histocompatibility Complex Class Typhoid Fever Major Histocompatibility Complex Molecule Cell Repertoire 
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. Adorini, L. Muller, S., Cardinaux, F., Lehmann, P.V., Falcioni, F. and Nagy Z.A. 1988. In vivo competition between self peptides and foreign antigens in T-cell activation. Nature, 334, 623 – 625.PubMedCrossRefGoogle Scholar
  2. Allen, P.M. 1987. Antigen processing at the molecular level. Immunol. Today, 8, 270 – 273.Google Scholar
  3. Allen, P.M., Babbit, B.P. and Unanue, E.R. 1987. T-cell recognition of lysosyme: the biochemical basis of presentation. Immunol. Rev., 98, 171 – 187.Google Scholar
  4. Benacerraf, B. and McDevitt, H.O. 1972. Histocompatibility-linked immune resonse genes. A new class of egnes that controls the formation of specific immune response has been identified. Science, 175, 273 – 279.PubMedCrossRefGoogle Scholar
  5. Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger,Google Scholar
  6. J.L. and Wiley, D.C. 1987. Structure of the human class I histocompatibility antigen, HLA-A2. Nature, 329, 506 - 512.CrossRefGoogle Scholar
  7. Bjorkman, P.J., Saper, M.A., Samraoui, B., Bennett, W.S., Strominger,Google Scholar
  8. J.L. and Wiley, D.C. 1987. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature, 329, 512 – 518.CrossRefGoogle Scholar
  9. Brown, J.H., Jardetzky, T., Saper, M.A., Samraoui, B., Bjorkman, P.J. and Wiley, D.C. 1988. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature, 322, 845 – 850.CrossRefGoogle Scholar
  10. Buus, S., Sette, A., Colon, S.M., Miles, C. and Grey H.M. 1987. TheGoogle Scholar
  11. relation between Major Histocompatibility Complex (MHC) restriction and the capacity of la to bind immunogenic peptides. Science, 235, 1353–1358.Google Scholar
  12. De Vries, R.R.P., Meera Khan, P., Bernini, L.F., Van Loghem, E. and Van Rood, J.J. 1979. Genetic control of survival to epidemics? J.Immunogenet., 6, 271 – 287.PubMedCrossRefGoogle Scholar
  13. De Vries, R.R.P., Schreuder, G.M.Th., Naipal, A, D’Amaro, J. and VanGoogle Scholar
  14. Rood, J.J. Selection by typhoid and yellow fever epidemics witnessed by the HLA-DR locus. Immunobiology of HLA vol. 2: “Immunogenetics and histocompatibility” (Ed. B. Dupont), Springer Verlag, New York, in press.Google Scholar
  15. De Vries, R.R.P., Ottenhoff, T.H.M. and Van Schooten, W.C.A. HLA andGoogle Scholar
  16. mycobacterial disease. In “Immunology of Mycobacterial Disease” (Ed. P.J. Lachmann). (Springer Seminars in Immunopathology 10) in press.Google Scholar
  17. Figueroa, F., Günther, E. and Klein, J. 1988. MHC polymorphism pre-dating speciation. Nature, 335, 265 – 267.PubMedCrossRefGoogle Scholar
  18. Howard, J.C. 1988. How old is a polymorphism? Nature, 332, 588 – 590.PubMedCrossRefGoogle Scholar
  19. Hughes, A.L. and Nei, M. 1988. Pattern of nucleotide substitution atGoogle Scholar
  20. major histocompatibility complex class I loci reveals overdominant selection. Nature, 335, 167–170.Google Scholar
  21. Janeway, C.A. 1988. T-cell development. Accessories or coreceptors? Nature, 335, 208 – 210.PubMedCrossRefGoogle Scholar
  22. Marrack, P. and Kappler J. 1988. The T-cell repertoire for antigen and MHC. Immunol. Today, 9, 308 – 315.Google Scholar
  23. McConnel1, T.J., Talbot W.S., Mclndoe, R.A. and Wakeland, E.K. 1988. The origin of MHC class II gene polymorphism within the genus Mus. Nature, 332, 651 – 654.CrossRefGoogle Scholar
  24. Lawlor, D.A., Ward, F.E., Ennis, P.D., Jackson, A.P. and Parham, P. 1988. HLA-A and B polymorphisms predate the divergence of humans and chimpanzees. Nature, 335, 268 – 271.PubMedCrossRefGoogle Scholar
  25. Parham, P. 1988. Presentation and processing of antigens in Paris. Immunol. Today, 9, 65 – 68.Google Scholar
  26. Schwartz, R.H. 1985. Associations in T-cell activation. Nature, 317, 284 – 285.PubMedCrossRefGoogle Scholar

Copyright information

© ECSC,EAEC,Brussels and Luxembourg 1989

Authors and Affiliations

  • R. R. P. de Vries
    • 1
  1. 1.Department of Immunohaematology & Blood BankUniversity HospitalLeidenThe Netherlands

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