Evolution of Class I HLA Antigen Presenting Molecules

  • Peter Parham


Two types of cytolytic cells are believed to offer protection against viral. infections. Both cell types, the cytolytic T cell (CTL) and the natural. killer (NK) cell, function through interaction with class I HLA antigen presenting molecules 1,2. On viral. infection, human cells synthesize viral. proteins. Some fractions of these proteins are degraded by a large intracellular protease — the proteasome — and short peptides thus formed are pumped into the endosplamic reticulum (ER). In the ER, peptides of 8–12 amino acids in length associate with class I heavy chains and β2-microglobulin to form functional. class I antigen presenting molecules, which are then targeted to the plasma membrane via the Golgi apparatus and the normal. secretory pathway. Once at the cell surface, the viral. peptides bound by class I molecules can interact with the antigen receptors of circulating CD8+ T cell thereby stimulating a CTL response which will kill the infected cell (Figure 1).


Heavy Chain Major Histocompatibility Complex Class Severe Malaria Major Histocompatibility Complex Molecule Antigen Present Molecule 
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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  1. 1.
    A. Townsend and H. Bodmer. Antigen recognition by class I restricted T lymphocytes. Ann. Rev. Immunol. 7:601 (1989).CrossRefGoogle Scholar
  2. 2.
    W.J. Storkus and J.R. Dawson. Target structures involved in natural. killing (NK): characteristics, distribution, and candidate molecules. Crit. Rev. Immunol. 10:393 (1991).PubMedGoogle Scholar
  3. 3.
    H.G Ljunggren and K. Karre. In search of the ‘missing self’: MHC molecules and NK cell recognition [see comments]. Immunol. Today 11:237 (1990).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Trowsdale and R.D. Campbell. Physical. map of the human HLA region. Immunol. Today 9:34 (1988).CrossRefGoogle Scholar
  5. 5.
    D.A. Lawlor, J. Zemmour, P.D. Ennis and P. Parham. Evolution of class I MHC genes and proteins: from natural. selection to thymic selection. Annu. Rev. Immunol. 8:23 (1990).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Messer, J. Zemmour, H.T. Orr, P. Parham et al. HLA-J: A second inactivated Class I HLA Gene related to HLA-G and HLA-A: Implications for the evolution of the HLA-A related genes. J. Immunol. 148:4043 (1992).PubMedGoogle Scholar
  7. 7.
    J.C. Howard. Disease and evolution. Nature 352: 565 (1991).PubMedCrossRefGoogle Scholar
  8. 8.
    P.J. Bjorkman, M.A. Saper, B. Samraoui, W.S. Bennett, J.L. Strominger and D.C. Wiley. Structure of the human class I histocompatibility antigen, HLA-2. Nature 329:506 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    D.H. Fremont, M. Matsumura, E.A. Stura, P.A. Peterson et al. Crystal. structures of two viral. peptides in complex with murine MHC class I H-2Kb. Science 257:919 (1992).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Matsumara, D.H. Fremont, P.A. Peterson and I.A. Wilson. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 267:927 (1992).CrossRefGoogle Scholar
  11. 11.
    D.R. Madden,J.C. Gorga, J.L. Strominger and D.C. Wiley. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353:321 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    D. Grossberger and P. Parham. Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure. Immunogenetics 36:116 (1992).CrossRefGoogle Scholar
  13. 13.
    F.M. Karlhofer, R.K. Ribaudo and W.M. Yokoyama. MHC class I alloantigen specificity of Ly-49+ IL-2 activated natural. killer cells. Nature 358:66 (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    J.G. Bodmer, S.G.E. Marsh. E.D. Albert, W.F. Bodmer et al. Nomenclature for factors of the HLA system, 1991. in: HLA 1991: Proceedings of the Eleventh International. Histocompatiblity Workshop and Conference, Vol. 1, K. Tsuji, M. Aizawa and T. Sasazuki, eds., Oxford Science Publications, Oxford, New York, Tokyo, pp.17 (1992).Google Scholar
  15. 15.
    J.A. López de Castro. HLA-B27 and HLA-A2 subtypes: structure, evolution and function. Immunol. Today 10:239 (1989).CrossRefGoogle Scholar
  16. 16.
    K. Fleischhauer, N.A. Kernan, R.J. O’Reilly, B. Dupont et al. Bone marrow allograft rejection by T lymphocytes recognising a single amino acid difference in HLA-B44. New. Engl. J. Med. 323:1818 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Zemmour and P. Parham. HLA Class I nucleotide sequences 1992. Immunogenetics 37:239 (1993).PubMedCrossRefGoogle Scholar
  18. 18.
    G.E. Rodey and T.C. Fuller. Public epitopes and the antigenic structure of the HLA molecules. CRC Crit. Rev. Immunol. 7:229 (1987).Google Scholar
  19. 19.
    K. Kato, J.A. Trapani, J. Allopenna, B. Dupont, et al. Molecular analysis of the serologically defined HLA-Awl9 antigens: A genetically distinct family of HLA-A antigens comprising A29, A31 and Aw33 but probably not A30. J. Immunol. 143:3371 (1989).PubMedGoogle Scholar
  20. 20.
    J.D. Domena, W.H. Hildebrand, W.B. Bias and P. Parham. A sixth family of HLA-A alleles defined by HLA-A*8001. Tissue Antigens 42:156 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    G.C. Starling, J.A. Wikowski, L.S. Speerbrecher, S.K. McKinney, et al. A novel HLA-A*8001 allele identified in African American population. Hum. Immunol., in press (1993).Google Scholar
  22. 22.
    S. Rosen-Bronson, A.G. Wagner, D. Stewart, S. Herbert, et al. DNA sequencing of a new HLA-A allele using locus specific PCR amplification. Human Immunol., 34: suppl. 1, 18th Annual. ASHI Meeting Abstracts, Abstract B2.2.17, pp 15 (1992).CrossRefGoogle Scholar
  23. 23.
    M.A. Khan. An overview of clinical. spectrum and heterogeneity of spondyloarthropathies. In: Rheumatic Disease Clinics of North America. M.A. Khan, Guest editor, p1, (1992).Google Scholar
  24. 24.
    P.J. Bjorkman and P. Parham. Strucutre, function and diversity of class I major histocompatibility molecules. Ann. Rev. Biochem. 59:253 (1990).PubMedCrossRefGoogle Scholar
  25. 25.
    R. Benjamin and P. Parham. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol. Today 11:137 (1990).Google Scholar
  26. 26.
    H. Fussell, M. Thomas, J. Street and C. Darke. Serological. identification of a new HLA-B7 variant antigen — HLA-B7Qui. Submitted. (1993).Google Scholar
  27. 27.
    P. Reekers, A. Tiilikainen, C. Darke, A. Van der Horst, et al. Antigen Society No. 111, part 2: HLA-B7-like antigen (B703(BPOT), B7Qui, BDT, B7SL, B7x40, BRI, B41V). In: HLA 1991: Proceedings of the Eleventh International. Histocompatibility Workshop and Conference, Vol. I (Ed. K. Tsuji, M. Aizawa, T. Sasazuki). p 327. Oxford University Press, New York (1992).Google Scholar
  28. 28.
    W.H. Hildebrand, J.D. Domena, S.Y. Shen, S.G. Marsh, et al. The HLA-B7Qui antigen Is encoded by a subtype of HLA-B27. In preparation.Google Scholar
  29. 29.
    A.M. Wan, P. Ennis, P. Parham and N. Holmes. The primary structure of HLA-A32 suggests a region Involved in formation of the Bw4/Bw6 epitopes. J. Immunol. 137:3671 (1986).PubMedGoogle Scholar
  30. 30.
    A.V.S. Hill, C.E.M. Allsopp, D. Kwiatkowski, N.M. Anstey, et al. Common West African HLA antigens are associated with protection from severe malaria. Nature 352:595 (1991).PubMedCrossRefGoogle Scholar
  31. 31.
    A.V.S Hill, J. Elvin, A.C. Willis, M. Aidoo, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360:434 (1992).PubMedCrossRefGoogle Scholar
  32. 32.
    W.H. Hildebrand, J.A. Madrigal, M.P. Belich, J. Zemmour, et al. Serologic cross-reactivities poorly reflect allelic relationships in the HLA-B12 and HLA-B21 groups: Dominant epitopes of the α2 helix. J. Immunol. 149:3563 (1992).PubMedGoogle Scholar
  33. 33.
    M.P. Beiich, J.A. Madrigal, W.H. Hildebrand, J. Zemmour, et al. Unusual. HLA-B alleles in two tribes of Brazilian Indians. Nature 357:326 (1992).CrossRefGoogle Scholar
  34. 34.
    G. Kawaguchi, N. Kato, K. Kashiwase, S. Karaki, et al. Structural. analysis of HLA-B40 epitopes. Hum. Immunol. 36:193 (1993).PubMedCrossRefGoogle Scholar
  35. 35.
    D.I. Watkins, S.N. McAdam, X. Liu, C.R. Strang, et al. New recombinant HLA-B alleles in a tribe of South American Amerindians indicate rapid evolution of major histocompatibility complex class I loci. Nature 357:329 (1992).PubMedCrossRefGoogle Scholar
  36. 36.
    D.A. Lawlor, E. Warren, P. Taylor and P. Parham. Gorilla class I MHC alleles: comparison to human and chimpanzee class I. J. Exp. Med. 174:1491 (1991).PubMedCrossRefGoogle Scholar
  37. 37.
    A.L. Hughes and M. Nei. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167 (1988).PubMedCrossRefGoogle Scholar
  38. 38.
    F.L. Black. Interrelationships betwen Amerindian tribes of lower Amazonia as manifest by HLA haplotype disequilibria. Am. J. Hum. Genet. 36:1318 (1984).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Peter Parham
    • 1
  1. 1.Department of Cell Biology, Sherman Fairchild BuildingStanford UniverstiyStanfordUSA

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