Skip to main content

Abstract

In humans the HLA-D region was originally discovered by use of the mixed lymphocyte culture (MLC) test. This assay is based on coculturing lymphocyte suspensions of two unrelated individuals and actually measures the proliferative capacity of T lymphocytes. Normally one uses a so-called one way stimulation, meaning that one of the two cell populations has been inactivated, for instance, by irradiation. As a result the treated cells are unable to proliferate but still have the capacity to stimulate T cells of the second individual. Lymphocytes from HLA-identical siblings generally do not stimulate each other in the MLC whereas lymphocytes from HLA nonidentical individuals do. Since serologically typed HLA-A, -B and -C identical individuals could stimulate each others’ cells, the incompatibility measured in the MLC was assigned to the HLA-D locus on chromosome 6. MHC antigens are inherited in a codominant fashion and as a consequence a given individual may be heterozygous for its HLA-D region products. Lymphocytes derived from donors descending from consanguineous offspring may be truly homozygous for the HLA region. Such homozygous typing cells (HTCs) were initially used to investigate and to inventory the polymorphism of HLA-D locus products. By now, more than 20 different HLA-D specificities have been identified in the human population. In parallel, MLC stimulating determinants have been documented for the chimpanzee and rhesus macaque (Jonker and Balner 1980). An apparently new set of antigens was defined using sera from multiparous women from which all HLA-A, -B and -C reactivity had been depleted. These allo-antisera reactions were found to have good concordance with HLA-D alleles but, moreover, were able to inhibit MLC reactivity. The serologically defined B lymphocyte cell surface antigens detected in this way were designated HLA-DR, standing for HLA-D related.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Andersson G, Larhammar D, Widmark E, Servenius B, Peterson PA, Rask L. Class II genes of the human major histocompatibility complex: organization and evolutionary relationship of the DRĂź genes. J Biol Chem 262: 8748–8758, 1987

    PubMed  CAS  Google Scholar 

  • Balner H, Gabb BW, Dersjant H, van Vreeswijk W, van Rood JJ. Major histocompatibility locus of rhesus monkeys (RhL-A). Nature 230: 177–180, 1971

    Article  Google Scholar 

  • Balner H, Gabb BW, D’Amaro J, van Vreeswijk W, Visser TP. Evidence for two linked loci controlling the serologically defined leukocyte antigens of chimpanzees (ChL-A). Tissue Antigens 4: 313–328, 1974

    Article  PubMed  CAS  Google Scholar 

  • Balner H, van Vreeswijk W, D’Amaro J, Roger J, Schreuder I, van Rood JJ. Chimpanzees share B cell as well as SD antigens with man. In: Bodmer WF, Batchelor JR, Bodmer JG, Festenstein H, Morris PJ (eds) Histocompatibility testing 1977. Munksgaard, Copenhagen, p 412, 1977

    Google Scholar 

  • Bergström T, Gyllensten U: Evolution of Mhc class II polymorphism: the rise and fall of class II gene fuction in primates. Immunol Rev 143: 13–32, 1995

    Article  PubMed  Google Scholar 

  • Bodmer JG, Marsh SGE, Albert ED, Bodmer WF, Bontrop RE, Charron D, Dupont B, Erlich HA, Mach B, Mayr WR, Parham P, Sasazuki T, Schreuder GMT, Strominger JL, Svejgaard A, Terasaki P. Nomenclature for factors of the HLA system 1995. Tissue Antigens 46: 1–18, 1995

    Article  PubMed  CAS  Google Scholar 

  • Böhme J, Andersson M, Andersson G, Moller E, Peterson PA, Rask L. HLA-DR beta genes vary in number between different DR specificities whereas the number of DQ beta genes is constant. J Immunol 135: 2149–2155, 1985

    PubMed  Google Scholar 

  • Bontrop RE, Schreuder GMT, Elferink BG, Mikulski MMA, Geerse R, Giphart MJ. Molecular serologic and functional evidence for an apparent HLA-DR triplet. J Immunol 137: 211–216, 1986a

    CAS  Google Scholar 

  • Bontrop RE, Schreuder GMT, Mikulski EMA, van Miltenburg RT, Giphart MJ. Polymorphisms within the HLA-DR4 haplotypes; various DQ subtypes detected with monoclonal antibodies. Tissue Antigens 27: 22–31, 1986b

    Article  CAS  Google Scholar 

  • Bontrop RE, Elferink BG, Otting N, Jonker M, de Vries RRP. Major histocompatibility complex class II restricted antigen presentation across a species barrier: conservation of restriction determinants in evolution. J Exp Med 172: 53–59, 1990a

    Article  CAS  Google Scholar 

  • Bontrop RE, Broos LAM, Pham K, Bakas RM, Otting Nand Jonker M. The chimpanzee major histocompatibility complex class II DR subregion contains an unexpectedly high number of beta-chain genes. Immunogenetics 32: 272–280, 1990b

    Article  CAS  Google Scholar 

  • Bontrop RE, Kenter M, Otting N, Jonker M. Major histocompatibility complex polymorphisms in humans and chimpanzees. J Med Primatol 22: 50–59, 1993

    PubMed  CAS  Google Scholar 

  • Bontrop RE, Otting N, Slierendregt BL, Lanchbury JS. Evolution of major histocompatibility complex polymorphisms and T-cell receptor diversity in primates. Immunol Rev 143: 32–62, 1995

    Article  Google Scholar 

  • Brändle U, Ono H, Vincek V, Klein D, Golubic M, Grahovac B, Klein J. Trans species evolution of Mhc-DRB haplotype polymorphism in primates: organization of DRB genes in the chimpanzee. Immunogenetics 36: 39–48, 1992

    Article  PubMed  Google Scholar 

  • Cairns JS, Curtsinger JM, Darl CA, Freeman S, Alter BJ, Bach FH. Sequence polymorphism of HLA-DRB1 alleles relating to T cell recognized determinants. Nature 317: 166–168, 1985

    Article  PubMed  CAS  Google Scholar 

  • Corell A, Morales P, Varela P, Paz-Artal E, Martin-Villa JM, Martinez-Laso J, Arnaiz-Villena A. Allelic diversity at the primate major histocompatibility complex DRB6 locus. Immunogenetics 36: 33–38, 1992

    Article  PubMed  CAS  Google Scholar 

  • Fan WM, Kasahara M, Gutknecht J, Klein D, Mayer WE, Jonker M, Klein J. Shared class II MHC polymorphisms between humans and chimpanzees. Hum Immunol 26: 107–121, 1989

    Article  PubMed  CAS  Google Scholar 

  • Figueroa F, O’hUigin C, Inoko H, Klein J. Primate DRB6 pseudogenes-clue to the evolutionary origin of the HLA-DR2 haplotype. Immunogenetics 34: 324–337, 1991

    Article  PubMed  CAS  Google Scholar 

  • Figueroa F, O’hUigin C, Tichy H, Klein J. The origin of the primate Mhc-DRB genes and allelic lineages as deduced from the study of prosimians. J Immunol 152: 4455–4465, 1994

    PubMed  CAS  Google Scholar 

  • Geluk A, Elferink BG, Slierendregt BL, van Meijgaarden KE, de Vries RRP, Ottenhoff THM, Bontrop RE. Evolutionary conservation of major histocompatibility complex- DR/peptide/T cell interactions in primates. J Exp Med 177: 979–984, 1993

    Article  PubMed  CAS  Google Scholar 

  • Gorski J. The HLA-DRw8 lineage was generated by a deletion in the DRB region followed by first domain diversification. J Immunol 142:4041–4045, 1989

    PubMed  CAS  Google Scholar 

  • Grahovac B, Mayer WE, Vincek V, Figueroa F, O’hUigin C, Tichy H, Klein J. Major histocompatibility complex DRB genes of a New-World monkey, the cottontop tamarin (Saguinus oedipus). Mol Biol Evol 9: 403–416, 1992

    PubMed  CAS  Google Scholar 

  • Gyllensten U, Sundvall M, Ezcurra I, Erlich HA. Genetic diversity at class II DRB loci of the primate MHC. J Immunol 146: 4368–4376, 1991

    PubMed  CAS  Google Scholar 

  • Gyllensten U, Bergstrom T, Josefson A, Sundvall M, Savage A, Blumer ES, Giraldo LH, Soto LH, Watkins DI. The cotton-top tamarin revisted: Mhc class I polymorphism of wild tamarins and polymorphism and allelic diversity of the class II DQA1, DQB1 and DRB loci. Immunogenetics 40: 167–176, 1994

    Article  PubMed  CAS  Google Scholar 

  • Heise ER, Cooke DJ, Schepart BS, Manning CH, McMahan MR, Chedid M, Keever CA. The major histocompatibility complex of primates. Genetica 73: 53–68, 1987

    PubMed  CAS  Google Scholar 

  • Hughes AL, Nei M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci USA 86: 958–962, 1989

    Article  PubMed  CAS  Google Scholar 

  • Jonker M, Balner H. Current knowledge of the D/DR region of the major histocompatibility complex of rhesus monkeys and chimpanzees. Hum Immunol 1: 305–316, 1980

    Article  PubMed  CAS  Google Scholar 

  • Kasahara M, Klein D, Fan W, Gutknecht J. Evolution of the class II major histocompatibility complex alleles in higher primates. Immunol Rev 113: 65–82, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kasahara M, Klein D, Vincek V, Sarapata DE, Klein J. Comparative anatomy of the primate major histocompatibility complex DR subregion: evidence for combinations of DRB genes conserved across species. Genomics 14: 340–349, 1992

    Article  PubMed  CAS  Google Scholar 

  • Kaufman JF, Auffray C, Korman AJ, Shackelford DA, Strominger JL. The class II molecules of the major histocompatibility complex. Cell 36: 1–13, 1984

    Article  PubMed  CAS  Google Scholar 

  • Kenter M, Otting N, Anholts J, Jonker M, Schipper R, Bontrop RE. Mhc-DRB diversity of the chimpanzee (Pan troglodytes). Immunogenetics 37: 1–11, 1992

    Article  PubMed  CAS  Google Scholar 

  • Kenter M, Otting N, de Weers M, Anholts J, Reiter C, Jonker M, Bontrop RE. Mhc- DRB and -DQA1 nucleotide sequences of three lowland gorillas: implications for the evolution of primate Mhc class II haplotypes. Hum Immunol 36: 205–218, 1993

    Article  PubMed  CAS  Google Scholar 

  • Klein D, Vincek V, Kasahara M, Shönbach C, O’hUigin C, Klein J. Gorilla major histocompatibility complex-DRB pseudogene orthologous to HLA-DRVIII. Hum Immunol 32: 211–220, 1991

    Article  PubMed  CAS  Google Scholar 

  • Klein J, O’hUigin C. Class II B Mhc motifs in an evolutionary perspective. Immunol Rev 143: 89–111, 1995

    Article  PubMed  CAS  Google Scholar 

  • Klein J, Bontrop RE, Dawkins RL, Erlich HA, Gyllensten UB, Heise ER, Jones PP, Parham P, Wakeland EK, Watkins DI. Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31: 217–219, 1990

    PubMed  CAS  Google Scholar 

  • Klein J, O’hUigin C, Figueroa F, Mayer WE, Klein D. Different modes of evolution in primates. Mol Biol Evol 10: 48–59, 1993

    PubMed  CAS  Google Scholar 

  • KĂĽpfermann H, Mayer WE, O’hUigin C, Klein D, Klein J. Shared polymorphism between gorilla and human major histocompatibility complex DRB loci. Hum Immunol 34: 267–278, 1992

    Article  PubMed  Google Scholar 

  • Larhammar D, Servenius B, Rask L, Peterson PA. Characterization of an HLA-DRB pseudo-gene. Proc Nail Acad Sci USA 82: 1475–1479, 1985

    Article  CAS  Google Scholar 

  • Lekutis C, Letvin NL. Biochemical and molecular characterization of rhesus monkey major histocompatibility complex class II DR. Hum Immunol 43: 72–80, 1995

    Article  PubMed  CAS  Google Scholar 

  • Mayer WE, O’hUigin C, Zaleska RZ, Klein J. Trans-species origin of Mhc-DRB polymorphism in the chimpanzee. Immunogenetics 37: 12–23, 1992

    Article  PubMed  CAS  Google Scholar 

  • Mayer WE, O’hUigin C, Klein J. Resolution of the HLA-DRB6 puzzle: a case of grafting a de novo-generated exon on an existing gene. Proc Nail Acad Sci USA 90: 10720–10724, 1993

    Article  CAS  Google Scholar 

  • McAdam SN, Boyson JE, Liu X, Garber TL, Hughes AL, Bontrop RE, Watkins DI. Chimpanzee MHC class I A locus alleles are related to only one of the six families of human A locus alleles. J Immunol 154: 6421–6429, 1995

    PubMed  CAS  Google Scholar 

  • Meunier HF, Carson S, Bodmer WF, Trowsdale J. An isolated Ăź1 exon next to the DRα gene in the HLA-D region. Immunogenetics 23: 172–180, 1986

    Article  PubMed  CAS  Google Scholar 

  • Mñuková-Fajdelová F, Satta Y, O’hUigin C, Mayer W, Figueroa F, Klein J. Alu elements of the primate major histocompatibility complex. Mammalian Genome 5: 405–415, 1994

    Article  PubMed  Google Scholar 

  • Nepom BS, Nepom GT, Mickelson E, Antonelli P, Hansen JA. Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between β chain diversity and HLA-D. Proc Natl Acad Sci USA 80: 6962–6966, 1983

    Article  PubMed  CAS  Google Scholar 

  • O’hUigin C, Bontrop R, Klein J. Nonhuman primate Mhc-DRB sequences: a compilation. Immunogenetics 38: 165–183, 1993

    PubMed  Google Scholar 

  • Rollini P, Mach B, Gorski J. Linkage map of three HLA-DR 13- chain genes: evidence for a recent duplication event. Proc Natl Acad Sci USA 82: 7179–7183, 1985

    Article  Google Scholar 

  • Schönbach C, Vincek V, Mayer WE, Golubic M, O’hUigin C, Klein J. Multiplication of Mhc-DRB5 loci in the orangutan: implications for the evolution of DRB haplotypes. Mammalian Genome 4: 159–170, 1993

    Article  PubMed  Google Scholar 

  • Slierendregt BL, Bontrop RE. Current knowledge on the major histocompatibility complex class II region in nonhuman primates. Eur J Immunogenet 21: 391–402, 1994

    Article  PubMed  CAS  Google Scholar 

  • Slierendregt BL, Otting N, Jonker M, Bontrop RE. RFLP analysis of the rhesus monkey MHC class II DR subregion. Hum Immunol 30: 11–17, 1991

    Article  PubMed  CAS  Google Scholar 

  • Slierendregt BL, van Noort JT, Bakas RM, Otting N, Jonker M, Bontrop RE. Evolutionary stability of trans-species major histocompatibility complex class II DRB lineages in humans and rhesus monkeys. Hum Immunol 35: 29–39, 1992

    Article  PubMed  CAS  Google Scholar 

  • Slierendregt BL, Kenter M, Otting N, Anholts J, Jonker M, Bontrop RE. Major histocompatibility complex class II haplotypes in a breeding colony of chimpanzees (Pan troglodytes). Tissue Antigens 42: 55–61, 1993

    PubMed  CAS  Google Scholar 

  • Slierendregt BL, Otting N, Van Besouw N, Jonker M, Bontrop RE. Expansion and contraction of rhesus macaque DRB regions by duplication and deletion. J Immunol 154: 2298–2307, 1994

    Google Scholar 

  • Slierendregt BL, Otting N, Jonker M, Bontrop RE. Gel electrophoretic analysis of rhesus macaque major histocompatibility complex class II DR molecules. Hum Immunol 40: 33–40, 1995

    Article  Google Scholar 

  • Sutton VR, Kienzle BK, Knowles RW. An altered splice site is found in the DRB4 gene that is not expressed in HLA-DR7Dwll individuals. Immunogenetics 29: 317–322, 1989

    Article  PubMed  CAS  Google Scholar 

  • Termijtelen A, van Leeuwen A, van Rood JJ. HLA-linked lymphocyte activating determinants. Immunol Rev 66: 79–101, 1982

    Article  PubMed  CAS  Google Scholar 

  • Trtková K, Kupfermann H, Grahovac B, Mayer WE, O’hUigin C, Tichy H, Bontrop R, Klein J. Mhc-DRB genes of platyrrhine primates. Immunogenetics 38: 210–222, 1993

    Article  PubMed  Google Scholar 

  • Watkins DI, Garber TL, Chen ZW, Toukatly G, Hughes AL, Letvin NL. Unusually limited nucleotide sequence variation of the expressed major histocompatibility complex class I genes of New World primate species (Saguinus oedipus). Immunogenetics 33: 79–89, 1991

    PubMed  CAS  Google Scholar 

  • Zhu Z, Vincek V, Figueroa F, Schönbach C, Klein J. Mhc-DRB genes of the pigtail macaque (Macaca nemestrina): implications for the evolution of human DRB genes. Mol Biol Evol 8: 563–578, 1991

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bontrop, R.E. (1997). Mhc Class II Genes of Nonhuman Primates. In: Blancher, A., Klein, J., Socha, W. (eds) Molecular Biology and Evolution of Blood Group and MHC Antigens in Primates. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59086-3_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59086-3_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63843-5

  • Online ISBN: 978-3-642-59086-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics