, Volume 27, Issue 2, pp 110–120

Characterization of the MHC class II region in cattle. The number of DQ genes varies between haplotypes

  • Leif Andersson
  • Lars Rask


The organization of the major histocompatibility complex (MHC) class II region in cattle was investigated by Southern blot analysis using human probes corresponding to DO, DP, DQ, and DR genes. Exon-specific probes were also employed to facilitate the assessment of the number of different bovine class II genes. The results indicated the presence of single DOβand DRαgenes, at least three DRβgenes, while the number of DQ genes was found to vary between MHC haplotypes. Four DQ haplotypes, DQα1β1 to DQα2β4, possessed a single DQα and a single DQβgene whereas both these genes were duplicated in eight other haplotypes, DQα3β5 to DQα9β12. No firm evidence for the presence of bovine DP genes was obtained. The same human probes were also used to investigate the genetic polymorphism of bovine class II genes. DQα DQβ, DRα DRβ, and DOβ restriction fragment length polymorphisms (RFLPs) were resolved and in particular the DQ restriction fragment patterns were highly polymorphic. Comparison of the present result with the current knowledge of the class II region in other mammalian species suggested that the DO, DP, DQ, DR, and DZ subdivision of the class II region was established already in the ancestor of mammals. The DP genes appear to be the least conserved class II genes among mammalian species and may have been lost in cattle. The degree of polymorphism of different class II genes, as revealed by RFLP analyses, shows striking similarities between species.


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  1. Alexander, A. J., Bailey, E., and Woodward, J. G.: Analysis of the equine lymphocyte antigen system by Southern blot hybridization. Immunogenetics 25: 47–54, 1987Google Scholar
  2. Amorena, B. and Stone, W. H.: Serologically defined (SD) locus in cattle. Science 201: 159–160, 1978Google Scholar
  3. Andersson, L., Böhme, J., Rask, L., and Peterson, P. A.: Genomic hybridization of bovine major histocompatibility genes. I. Extensive polymorphism of DQα and DQβ genes. Anim. Genet. 17: 95–112, 1986aGoogle Scholar
  4. Andersson, L., Böhme, J., Peterson, P. A., and Rask, L.: Genomic hybridization of bovine major histocompatibility genes. II. Polymorphism of DR genes and linkage disequilibrium in the DQ-DR region. Anim. Genet. 17: 295–304, 1986bGoogle Scholar
  5. Andersson, G., Larhammar, D., Widmark, E., Servenius, B., Peterson, P. A., and Rask, L.: Class II genes of the human major histocompatibility complex. Organization and evolution of the DRβ genes. J. Biol. Chem. 262: 8748–8758, 1987aGoogle Scholar
  6. Andersson, L., Lundberg, C., Rask, L., Gissel-Nielsen, B., and Simonsen, M.: Analysis of class II genes of the chicken MHC (B) by use of human DNA probes. Immunogenetics 26: 79–84, 1987bGoogle Scholar
  7. Andersson, L., Pääbo, S., Rask, L.: Is allograft rejection a clue to the mechanism promoting MHC polymorphism? Immunol. Today 8: 206–209, 1987cGoogle Scholar
  8. Benacerraf, B. and Germain, R. N.: The immune response genes of the major histocompatibility complex. Immunol. Rev. 38: 70–119, 1978Google Scholar
  9. Bodmer, W. F.: Evolutionary significance of the HL-A system. Nature 237: 139–183, 1972Google Scholar
  10. Böhme, J., Andersson, M., Andersson, G., Möller, E., Peterson, P. A., and Rask, L.: HLA-DR β genes vary in number between different DR specificities, whereas the number of DQ β genes is constant. J. Immunol. 135: 2149–2155, 1985Google Scholar
  11. Bukara, M., Vincek, V., Figueroa, F., and Klein, J.: How polymorphic are class II loci of the mouse H-2 complex? Immunogenetics 21: 569–579, 1985Google Scholar
  12. Caldwell, J.: Polymorphism of the BoLA system. Tissue Antigens 13: 319–326, 1979Google Scholar
  13. Church, G. M. and Gilbert, W.: Genomic sequencing. Proc. Natl. Acad. Sci. U.S.A. 81: 1991–1995, 1984Google Scholar
  14. Denaro, M., Hammerling, U., Rask, L., and Peterson, P. A.: The Eβb gene may have acted as the donor gene in a gene conversion-like event generating the Aβbm12 mutant. EMBO J. 3: 2029–2032, 1984Google Scholar
  15. Giles, R. C. and Capra, J. D.: Structure, function and genetics of human class II molecules. Adv. Immunol. 37: 1–71, 1985Google Scholar
  16. Gorski, J. and Mach, B.: Polymorphism of human Ia antigens: gene conversion between two DRβ loci results in a new HLA-D/DR specificity. Nature 322: 67–70, 1986Google Scholar
  17. Gustafsson, K., Emmoth, E., Widmark, E., Böhme, J., Peterson, P. A., and Rask, L.: Isolation of a cDNA clone coding for an SB β-chain. Nature 309: 76–78, 1984aGoogle Scholar
  18. Gustafsson, K., Wiman, K., Emmoth, E., Larhammar, D., Böhme, J., Hyldig-Nielsen, J. J., Ronne, H., Peterson, P. A., and Rask, L.: Mutations and selection in the generation of class II histocompatibility antigen polymorphism. EMBO J. 3: 1655–1661, 1984bGoogle Scholar
  19. Gustafsson, K., Widmark, E., Servenius, B., Sachs, D. H., Larhammar, D., Peterson, P. A., and Rask, L.: Class II genes of the human major histocompatibility complex. Evolution of the DP region as deduced from nucleotide sequences of the four genes. J. Biol. Chem. 262: 8778–8786, 1987Google Scholar
  20. Hardy, D. A., Bell, J. I., Long, E. O., Lindsten, T., and McDevitt, H. O.: Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature 323: 453–455, 1986Google Scholar
  21. Hoang-Xuan, M., Charron, D., Zilber, M.-T., and Levy, D.: Biochemical characterization of class II bovine major histocompatibility complex antigens using cross-species reactive antibodies. Immunogenetics 15: 621–624, 1982Google Scholar
  22. Jonsson, A.-K., Hyldig-Nielsen, J. J., Servenius, B., Larhammar, D., Andersson, G., Jörgensen, F., Peterson, P. A., and Rask, L.: Class II genes of the human major histocompatibility complex. Comparisons of DQ and DX a and β genes. J. Biol. Chem. 262: 8767–8777, 1987Google Scholar
  23. Kappes, D. J., Arnot, D., Okada, K., and Strominger, J. L.: Structure and polymorphism of the HLA class II SB light chain genes. EMBO J. 3: 2985–2993, 1984Google Scholar
  24. Klein, J.: Natural History of the Major Histocompatibility Complex, John Wiley and Son, New York, 1986Google Scholar
  25. Kobori, J. A., Strauss, E., Minard, K., and Hood, L.: Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex. Science 234: 173–179, 1986Google Scholar
  26. Larhammar, D., Gustafsson, K., Claesson, L., Bill, P., Wiman, K., Schenning, L., Sundelin, J., Widmark, E., Peterson, P. A., and Rask, L.: Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins. Cell 30: 153–161, 1982aGoogle Scholar
  27. Larhammar, D., Schenning, L., Gustafsson, K., Wiman, K., Claesson, L., Rask, L., and Peterson, P. A.: Complete amino acid sequence of an HLA-DR antigen-like β chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, B, and -C antigens. Proc. Natl. Acad. Sci. U.S.A. 79: 3687–3691, 1982bGoogle Scholar
  28. Larhammar, D., Hammerling, U., Rask, L., and Peterson, P. A.: Sequence of gene and cDNA encoding murine major histocompatibility complex class Il gene Aβ2. J. Biol. Chem. 260: 14111–14119, 1985Google Scholar
  29. McIntyre, K. R. and Seidman, J. G.: Nucleotide sequence of mutant I-Abm12 gene is evidence for genetic exchange between mouse immune response genes. Nature 308: 551–553, 1984Google Scholar
  30. Nagy, Z. A., Baxevanis, C. N., Ishii, N., and Klein, J.: Ia antigens as restriction molecules in Ir-gene controlled T-cell proliferation. Immunol. Rev. 60: 59–83, 1981Google Scholar
  31. Rask, L., Gustafsson, K., Larhammar, D., Ronne, H., and Peterson, P. A.: Generation of class II antigen polymorphism. Immunol. Rev. 84: 123–143, 1985Google Scholar
  32. Rask, L., Andersson, G., Andersson, L., Gustafsson, K., Jonsson, A.K., Larhammar, D., and Peterson, P. A.: The evolution of human class II antigens as deduced from sequence analysis. In G. Kelsoe and D. Schulze (eds.): Evolution and Vertebrate Immunity: The Antigen-Receptor and MHC Gene Family, pp. 363–377, The University of Texas Press, Texas, 1987Google Scholar
  33. Rigby, P. W. J., Dieckman, M., Rhodes, C., and Berg, P.: Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J. Mol. Biol. 113: 237–251, 1977Google Scholar
  34. Ryder, L. P., Svejgaard, A., and Dausset, J.: Genetics of HLA disease associations. Annu. Rev. Genet. 15: 169–187, 1981Google Scholar
  35. Schenning, L., Larhammar, D., Bill, P., Wiman, K., Jonsson, A.-K., Rask, L., and Peterson, P. A.: Both α and β chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains. EMBO J. 3: 447–452, 1984Google Scholar
  36. Schwarz, R. H.: T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu. Rev. Immunol. 3: 237–261, 1985Google Scholar
  37. Scott, P. C., Choi, C.-L., and Brandon, M. R.: Genetic organization of the ovine MHC class II region. Immunogenetics 25: 116–122, 1987Google Scholar
  38. Servenius, B., Gustafsson, K., Widmark, E., Emmoth, E., Andersson, G., Larhammar, D., Rask, L., and Peterson, P. A.: Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SBα (DPα) pseudogene. EMBO J. 3: 3209–3214, 1984Google Scholar
  39. Servenius, B., Rask, L., and Peterson, P. A.: Class II genes of the human major histocompatibility complex. The DOβ gene is a divergent member of the class II β gene family. J. Biol. Chem. 262: 8759–8766, 1987Google Scholar
  40. Sittisombut, N. and Knight, K. L.: Rabbit major histocompatibility complex. I. Isolation and characterization of three subregions of class II genes. J. Immunol. 136: 1871–1875, 1986Google Scholar
  41. Spooner, R. L., Leveziel, H., Grosclaude, F., Oliver, R. A., and Vaiman, M.: Evidence for a possible major histocompatibility complex (BLA) in cattle. J. Immunogenet. 5: 335–346, 1978Google Scholar
  42. Steinmetz, M., Stephan, D., and Fischer-Lindahl, K.: Gene organization and recombination hotspots in the murine major histocompatibility complex. Cell 44: 895–904, 1986Google Scholar
  43. Tonelle, C., DeMars, R., and Long, E. O.: DOβ is a new β chain gene in HLA-D with a distinct regulation of expression. EMBO J. 4: 2839–2847, 1985Google Scholar
  44. Treisman, M.: The significance of immunity restriction by the major histocompatibility complex, and of the occurrence of high polymorphism at MHC loci: two hypothesis. J. Theor. Biol. 89: 409–421, 1981Google Scholar
  45. Trowsdale, J. and Kelly, A.: The human HLA class II α chain gene DZα is distinct from genes in the DP, DQ and DR subregions. EMBO J. 4: 2231–2237, 1985Google Scholar
  46. Trowsdale, J., Young, J. A. T., Kelly, A. P., Austin, P. J., Carson, S., Meunier, H., So, A., Ehrlich, H. A., Spielman, R. S., Bodmer, J., and Bodmer, W. F.: Structure, sequence and polymorphism in the HLA-D region. Immunol. Rev. 85: 5–43, 1985Google Scholar
  47. Usinger, W. R., Curie-Cohen, M., and Stone, W. H.: Lymphocyte defined loci in cattle. Science 196: 1017–1018, 1977Google Scholar
  48. Wettstein, P. J. and States, J. S.: The major histocompatibility complex of tassel-eared squirrels. I. Genetic diversity associated with Kaibab squirrels. Immunogenetics 24: 230–241, 1986Google Scholar
  49. Widera, G. and Flavell, R. A.: The I region of the C57BL/10 mouse: characterization and physical linkage to H-2K of a novel SBβ-like class II pseudogene ΨAβ3. Proc. Natl. Acad. Sci. U.S.A. 82: 5500–5504, 1985Google Scholar
  50. Zinkernagel, R. M. and Doherty, P. C.: MHC-restricted T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function and responsiveness. Adv. Immunol. 27: 221–292, 1979Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Leif Andersson
    • 1
  • Lars Rask
    • 2
  1. 1.Department of Animal BreedingSwedish University of Agricultural SciencesUppsalaSweden
  2. 2.Department of Cell ResearchSwedish University of Agricultural SciencesUppsalaSweden

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