title: Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies.
abstract: The rhesus macaque is an important preclinical model in transplantation research and in investigations of chronic and infectious diseases that need a well-characterised major histocompatibility complex (MHC-Mamu). In a large population of pedigreed rhesus macaques, 70 Mamu-DRB, 18 -DQA1, 24 -DQB1, and 14 -DPB1 alleles were detected. In humans, five HLA-DRB region configurations are present, displaying diversity with regard to number and combinations of loci. The HLA-DRB1 gene of each of these configurations is highly polymorphic. For rhesus monkeys, at least 31 Mamu-DRB region configurations have been determined. In contrast to humans, most Mamu-DRB region configurations display no or only limited allelic polymorphism. Segregation analyses revealed 28 Mamu-DQA1/DQB1 pairs, each pair linked to a limited number of Mamu-DRB region configurations and vice versa. In comparison with humans, the degree of freedom of recombination between Mamu-DQA1 and -DQB1 is extremely low and equivalents of HLA-DQA2/DQB2 are absent. The Mamu-DPA1 gene is invariant and -DPB1 manifests only moderate allelic variation, whereas the HLA-DPA1 gene is oligomorphic and HLA-DPB1 highly polymorphic. Thus, both species used different evolutionary strategies to create polymorphism and diversity at the MHC class II loci in order to cope with pathogens.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands. doxiadis@bprc.nl
authors.forename: G G
authors.initials: GG
authors.lastname: Doxiadis
authors.forename: N
authors.initials: N
authors.lastname: Otting
authors.forename: N G
authors.initials: NG
authors.lastname: de Groot
authors.forename: R E
authors.initials: RE
authors.lastname: Bontrop
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005802:Genes, MHC Class II; D006239:Haplotypes; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics* / Q000276:immunology; D023421:Models, Animal; D011110:Polymorphism, Genetic