The MHC class I genes of the rhesus monkey. Different evolutionary histories of MHC class I and II genes in primates.

Abstract

Homologues of the human HLA-A and -B MHC class I loci have been found in great apes and Old World primates suggesting that these two loci have existed for at least 30 million years. The C locus, however, shows some sequence similarity to the B locus and has been found only in gorillas, chimpanzees, and humans. To determine the age of the MHC class I C locus and to examine the evolution of the A and B loci we have cloned, sequenced, and in vitro translated 16 MHC class I cDNAs from two unrelated rhesus monkeys (Macaca mulatta) using both cDNA library screening and PCR amplification. Analyses of these sequences suggest that the C locus is not present in the rhesus monkey, indicating that this locus may be of recent origin in gorillas, chimpanzees, and humans. The rhesus monkey's complement of MHC class I genes includes the products of at least one expressed A locus and at least two expressed B loci, indicating that a duplication of the B locus has taken place in the lineage leading to these Old World primates. Comparison of rhesus monkey MHC class I cDNAs to their primate counterparts reveals fundamental differences between MHC class I and class II evolution in primates. Although MHC class II allelic lineages are shared between humans and Old World primates, no such trans-species sharing of allelic lineages is seen at the MHC class I loci.

Nonhuman Primate Models for HIV/AIDS Vaccine Development

“…In contrast to the highly polymorphic genes of the major MHC class I genes in humans ( HLA ‐ A , HLA ‐ B , and HLA ‐ C ), the rhesus macaque MHC genes use an alternative strategy, i.e., they express multiple dominant Mamu ‐ A and Mamu‐B transcripts per chromosome with high expression levels. Rhesus macaques may possess one to three A and two to four B locus genes (Boyson et al, ; Urvater et al, ). In other words, rhesus macaques are characterized not only by alternative gene combinations, but also by diversity in gene number to ensure that different individuals mount distinct responses against the same pathogen (Otting et al, ).…”

MHC class I Ligands of Rhesus Macaque Killer-Cell Immunoglobulin-Like Receptors

“…In humans, the ligation of activating lineage III KIRs (KIR2DS) and KIR2DL4 on maternal NK cells of the placental decidua by HLA-C and soluble HLA-G stimulates the release of pro-inflammatory and pro-angiogenic factors that promote placental vascularization (20, 21, 45). Since macaques do not express orthologs of HLA-C or -G (28, 29, 38), it is conceivable that KIR3DS interactions with Mamu-AG play a similar role in placental development. Unlike human KIRs , which can be broadly categorized into inhibitory or activating haplotypes based on fixed differences in the number of activating genes, KIR haplotypes in macaques are much more variable (82).…”

“…In contrast to humans, which have three classical HLA class I genes ( HLA-A, -B and -C ), Old World monkeys express an expanded array of polymorphic MHC class I genes related to HLA-A and -B . However, these species do not have an HLA-C ortholog, since MHC-C arose in hominids as a duplication of an MHC-B gene after their divergence from Old World monkeys (28, 29). The MHC class I haplotypes of Old World monkeys are polygenic, and rhesus macaques typically express two or three Ma caca mu latta (Mamu)-A genes and 4-11 Mamu-B genes (30–32).…”

Molecular typing of major histocompatibility complex class I alleles in the Indian rhesus macaque which restrict SIV CD8+ T cell epitopes

“…Moreover, in contrast to the limited three highly polymorphic HLA-A, HLA-B, and HLA-C loci per haplotype in humans, any given rhesus chromosome can contain from 4 up to 14 functional class I loci (Daza-Vamenta et al 2004;Otting et al 2005;Shiina et al 2006). Presently, there is no evidence for a locus similar to HLA-C in the rhesus macaque, suggesting that the HLA-C locus is of a fairly recent origin in humans (Watkins et al 1988;Boyson et al 1996). While much is yet to be elucidated about the MHC of the rhesus macaque relative to the human, it appears that each species has evolved different, yet effective, strategies to ensure that the critical function of the MHC is maintained in the face of numerous pathogens (Otting et al 2005).…”

“…As the genomic organization of the MHC is similar in rhesus macaques (Macaca mulatta) and humans (Kelley et al 2005;Bontrop 2006), the rhesus macaque has been used extensively in biomedical research. While rhesus macaques express orthologues of MHC class I loci homologous to the HLA-A and HLA-B loci (Miller et al 1991;Boyson et al 1996), phylogenetic analysis clearly indicates that the great majority of rhesus classical MHC class I alleles cluster outside of and do not appear to be related to any of the classical human class I lineages (Boyson et al 1996). Moreover, in contrast to the limited three highly polymorphic HLA-A, HLA-B, and HLA-C loci per haplotype in humans, any given rhesus chromosome can contain from 4 up to 14 functional class I loci (Daza-Vamenta et al 2004;Otting et al 2005;Shiina et al 2006).…”