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.
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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 DRß genes. J Biol Chem 262: 8748–8758, 1987
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
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
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
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
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
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
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
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
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
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
Bontrop RE, Kenter M, Otting N, Jonker M. Major histocompatibility complex polymorphisms in humans and chimpanzees. J Med Primatol 22: 50–59, 1993
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Kaufman JF, Auffray C, Korman AJ, Shackelford DA, Strominger JL. The class II molecules of the major histocompatibility complex. Cell 36: 1–13, 1984
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
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
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
Klein J, O’hUigin C. Class II B Mhc motifs in an evolutionary perspective. Immunol Rev 143: 89–111, 1995
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
Klein J, O’hUigin C, Figueroa F, Mayer WE, Klein D. Different modes of evolution in primates. Mol Biol Evol 10: 48–59, 1993
Küpfermann 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
Larhammar D, Servenius B, Rask L, Peterson PA. Characterization of an HLA-DRB pseudo-gene. Proc Nail Acad Sci USA 82: 1475–1479, 1985
Lekutis C, Letvin NL. Biochemical and molecular characterization of rhesus monkey major histocompatibility complex class II DR. Hum Immunol 43: 72–80, 1995
Mayer WE, O’hUigin C, Zaleska RZ, Klein J. Trans-species origin of Mhc-DRB polymorphism in the chimpanzee. Immunogenetics 37: 12–23, 1992
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
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
Meunier HF, Carson S, Bodmer WF, Trowsdale J. An isolated ß1 exon next to the DRα gene in the HLA-D region. Immunogenetics 23: 172–180, 1986
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
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
O’hUigin C, Bontrop R, Klein J. Nonhuman primate Mhc-DRB sequences: a compilation. Immunogenetics 38: 165–183, 1993
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
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
Slierendregt BL, Bontrop RE. Current knowledge on the major histocompatibility complex class II region in nonhuman primates. Eur J Immunogenet 21: 391–402, 1994
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
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
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
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
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
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
Termijtelen A, van Leeuwen A, van Rood JJ. HLA-linked lymphocyte activating determinants. Immunol Rev 66: 79–101, 1982
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
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
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
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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
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DOI: https://doi.org/10.1007/978-3-642-59086-3_14
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