New Major Histocompatibility Complex Class IIB Genes From Nurse Shark

  • Simona Bartl
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 484)


The Major Histocompatibility Complex (MHC) codes for proteins that process and present antigens to T cells. The actual presenting proteins are the classical MHC molecules and they are subdivided into two classes, I and II. Each class of MHC protein has an antigen binding cleft (ABC) that is formed by two membrane distal domains and that binds processed peptides. Classical MHC proteins tend to be highly polymorphic with most variable sites clustered around the ABC. This polymorphism has an effect on the repertoire of peptides that can bind and on the T cell receptors (TCRs) selected in the thymus by each MHC molecule (1, 2). The polymorphism appears to be generated by point mutations and recombination events (3–8). Analyses of mammalian genes suggests that blocks of residues can be transferred between MHC alleles or loci by recombination. These blocks have been identified as hypervariable


Major Histocompatibility Complex Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Major Histocompatibility Complex Gene Major Histocompatibility Complex Allele 
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  1. 1.
    Robey E, Fowles BJ. Selective events in T cell development. Annu Rev Immunol 1994;12:675–705.PubMedCrossRefGoogle Scholar
  2. 2.
    Rothbard JB, Gefter ML. Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol 1991;9:527–565.PubMedCrossRefGoogle Scholar
  3. 3.
    Lawlor DA, Zemmour J, Ennis PD, Parham P. Evolution of class-I MHC genes and proteins: from natural selection to thymic selection. Annu Rev Immunol 1990;8:23–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Klein J, Satta Y, O’hUigin C, Takahata N. The molecular descent of the major histocompatibility complex. Annu Rev Immunol 1993;11:269–295.PubMedCrossRefGoogle Scholar
  5. 5.
    Gyllensten UB, Sundvall M, Erlich HA. Allelic diversity is generated by intraexon sequence exchange at theDRBIlocus of primates. Proc Natl Acad Sci USA 1991;88:3686–3890.PubMedCrossRefGoogle Scholar
  6. 6.
    Gaur LK, Nepom GT. Ancestral major histocompatibility complexDRBgenes beget conserved patterns of localized polymorphisms. Proc Natl Acad Sci USA 1996;93:5380–5383.PubMedCrossRefGoogle Scholar
  7. 7.
    Brunsberg U, Edfors-Lilja I, Andersson L, Gustafsson K. Structure and organization of pigMHCclass IIDRBgenes: evidence for genetic exchange between loci. Immunogenetics 1996;44:1–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Ohta T. On the pattern of polymorphisms at major histocompatibility complex loci. J Mol Evol 1998;46:633–638.PubMedCrossRefGoogle Scholar
  9. 9.
    Lundberg AS, McDevitt HO. Evolution of major histocompatibility complex class II allelic diversity: Direct descent in mice and humans. Proc Natl Acad Sci USA 1992;89:6545–6549.PubMedCrossRefGoogle Scholar
  10. 10.
    Madden DR, Gorga JC, Strominger JL, Wiley DC. The three-dimensional structure of HLA-B27 at 2–1A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 1992;70:1035–1048.PubMedCrossRefGoogle Scholar
  11. 11.
    Brown JH, et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DRI. Nature 1993;364:33–39.PubMedCrossRefGoogle Scholar
  12. 12.
    Bartl S. What sharks can tell us about the evolution of MHC genes. Immunol Rev 1998;166:317332.Google Scholar
  13. 13.
    Klein J. Natural History of the Major Histocompatibility Complex. New York:Wiley and Son; 1986.Google Scholar
  14. 14.
    Trowsdale J. “Both man & bird & beast”: comparative organization of MHC genes. Immunogenetics 1995; 41:1–17.PubMedCrossRefGoogle Scholar
  15. 15.
    Jones EY. MHC class I and class II structures. Curr Opin Immunol 1997;9:75–79.PubMedCrossRefGoogle Scholar
  16. 16.
    Kroppshofer H, Hammerling GJ, Vogt AB. How HLA-DM edits the MHC class II peptide repertoire: survival of the fittest? Immunol Today 1997;18:77–82.CrossRefGoogle Scholar
  17. 17.
    Kropshofer H, Vogt AB, Moldenhauer G, Hammer J, Blum JS, Hammerling GJ. Editing of the HLA-DR-peptide repertoire by HLA-DM. EMBO J 1996;15:6144–6154.PubMedGoogle Scholar
  18. 18.
    Vogt AB, Moldenhauer G, Hammerling GJ, Kropshofer H. HLA-DM stabilizes empty HLA-DR molecules in a chaperone-like fashion. Immunol Lett 1997;57:209–211.PubMedCrossRefGoogle Scholar
  19. 19.
    Kropshofer H, Vogt AB, Thery C, Armandola EA, Li BC, Moldenhauer G, Amigorena S, Hammerling GJ. A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules. EMBO J 1998;17:2971–2981.PubMedCrossRefGoogle Scholar
  20. 20.
    Liljedahl M, Kuwana T, Fung-Leung WP, Jackson MR, Peterson PA, Karlsson L. HLA-DO is a lysosomal resident which requires association with HLA-DM for efficient intracellular transport. EMBO J 1996;15:4817–4824.PubMedGoogle Scholar
  21. 21.
    Parham P. The rise and fall of great class I genes. Semin Immunol 1994;6:373–382.PubMedCrossRefGoogle Scholar
  22. 22.
    Kasahara M, Flajnik MF, Ishibashi T, Natori T. Evolution of the major histocompatibility complex: a current overview. Transplant Immunology 1995;3:1–20.PubMedCrossRefGoogle Scholar
  23. 23.
    Bartl S, Weissman IL. Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark. Proc Natl Acad Sci USA 1994;91:262–266.PubMedCrossRefGoogle Scholar
  24. 24.
    Lawlor DA, Ward FE, Ennis PD, Jackson AP, Parham P. HLA-A and B polymorphisms predate the divergence of humans and chimpanzees. Nature 1988;335:268–271.PubMedCrossRefGoogle Scholar
  25. 25.
    Kelley AP, Monaco JJ, Cho S, Trowsdale J. A new human HLA class II-related locusDM.Nature 1991;353:571–573.CrossRefGoogle Scholar
  26. 26.
    Cho S, Attaya M, Monaco JJ. New class II-like genes in the murine MHC. Nature 1991;353:573–576.PubMedCrossRefGoogle Scholar
  27. 27.
    Niimi M, Nakai Y, Aida Y. Nucleotide sequences and the molecular evolution of the DMA and DMB genes of the bovine major histocompatibility complex. Biochem Biophys Res Commun 1995;217:522–528.PubMedCrossRefGoogle Scholar
  28. 28.
    Tonnelle C, DeMars R, Long EO. DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression. EMBO J 1985;4:2839–2847.PubMedGoogle Scholar
  29. 29.
    Servenius B, Rask L, Peterson PA. Class II genes of the human major histocompatibility complex. The DO beta gene is a divergent member of the class II beta gene family. J Biol Chem 1987;262:8759–8766.PubMedGoogle Scholar
  30. 30.
    Wright H, Redmond J, Ballingall KT. The sheep orthologue of the HLA-DOB gene. Immunogenetics 1996;43:76–79.PubMedGoogle Scholar
  31. 31.
    Larhammar D, Hammerling U, Rask L, Peterson PA. Sequence of gene and eDNA encoding murine major histocompatibility complex class II gene A beta 2. J Biol Chem 1985;260:14111–14119.PubMedGoogle Scholar
  32. 32.
    Williams AF, Barclay AN. The immunoglobulin superfamily-domains for cell surface recognition. Ann Rev Immunol 1988;6:381–405.CrossRefGoogle Scholar
  33. 33.
    König R, Huang L-Y, Germain RN. MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8. Nature 1992;356:796–798.PubMedCrossRefGoogle Scholar
  34. 34.
    Cammarota G, et al. Identification of a CD4 binding site on the ß2 domain of HLA-DR molecules. Nature 1992;356:799–801.PubMedCrossRefGoogle Scholar
  35. 35.
    Graser R, O’hUigin C, Vincek V, Meyer A, Klein J. Trans-species polymorphism of class IIMhcloci in danio fishes. Immunogenetics 1996;44:36–48.PubMedCrossRefGoogle Scholar
  36. 36.
    Brown JH, Jardetzky T, Saper MA, Samraoui B, Bjorkman PJ, Wiley DC. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature 1988;332:845–850.PubMedCrossRefGoogle Scholar
  37. 37.
    Ohta T. On the evolution of multigene families. Theor Popul Biol 1983;23:216–240.PubMedCrossRefGoogle Scholar
  38. 38.
    Okamura K, Ototake M, Nakanishi T, Kurosawa Y, Hashimoto K. The most primitive vertebrates with jaws possess highly polymorphic MHC class I genes comparable to those of humans. Immunity 1997;7:777–790.PubMedCrossRefGoogle Scholar
  39. 39.
    Bartl S, Baish MA, Flajnik MF, Ohta Y. Identification of class I genes in cartilaginous fish, the most ancient group of vertebrates displaying an adaptive immune response. J Immunol 1997;159:6097–6104.PubMedGoogle Scholar
  40. 40.
    Kasahara M, McKinney EC, Flajnik MF, Ishibashi T. The evolutionary origin of the major histocompatibility complex: polymorphism of class II a chain genesinthe cartilaginous fish. Eur J Immunol 1993;23:2160–2165.PubMedCrossRefGoogle Scholar
  41. 41.
    Hansen JD, Strassburger P, Du Pasquier L. Conservation of an alpha 2 domain within the teleostean world, MHC class I from the rainbow troutOncorhynchus myldss.Dev Comp Immunol 1996;20:417–425.PubMedCrossRefGoogle Scholar
  42. 42.
    Saitou N, Nei M. The neighbor-joining method: A new method for constructing phylogenetic trees. Mol Biol Evol 1987;4:406–425.PubMedGoogle Scholar
  43. 43.
    Málaga-Trillo E, et al. Linkage relationships and haplotype polymorphism among cichlidMhcclass IIBloci. Genetics 1998;149:1527–1537.PubMedGoogle Scholar
  44. 44.
    Saito H, Maki RA, Clayton LK, Tonegawa S. Complete primary structures of the E 13 chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci USA 1983;80:5520–5524.CrossRefGoogle Scholar
  45. 45.
    Estess P, Begovich AB, Koo M, Jones PP, McDevitt HO. Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta eDNA clones. Proc Natl Acad Sci USA 1986;83:3594–3598.PubMedCrossRefGoogle Scholar
  46. 46.
    Sato K, Flajnik MF, Du Pasquier L, Katagiri M, Kasahara M. Evolution of the MHC: isolation of class II (3-chain cDNA clones from the amphibian Xenopus lacvis. J Immunol 1993;150:2831–2843.PubMedGoogle Scholar
  47. 47.
    Ono H, et al. Major histocompatibility complex class II genes of zcbrafish. Proc Natl Acad Sci USA 1992;89:11886–11890.PubMedCrossRefGoogle Scholar
  48. 48.
    Hordvik I, Grimholt U, Fosse VM, Lie0Endresen C. Cloning and sequence analysis of cDNAs encoding the MHC class II (i chain in Atlantic salmon(Salmo salar). Immunogenetics 1993;37:437–441.PubMedCrossRefGoogle Scholar
  49. 49.
    Klein D, Ono H, O’hUigin C, Vincek V, Goldsclunidt T, Klein J. Extensive MHC variability in cichlid fishes of Lake Malawi. Nature 1993;364:330–334.PubMedCrossRefGoogle Scholar
  50. 50.
    Dixon B, Stet PJM, van Erp SHM, Pohajdak 13. Characterization of (32-microglobulin gene in the zebrafish. Immunogenetics 1993;38:27–34.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Simona Bartl
    • 1
  1. 1.Moss Landing Marine Laboratories

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