The MHC and TCR genes of nonhuman primates

The products of the MHC and TCR genes represent some of the most important molecules involved in initiating and controlling an immune response against a pathogen. Although various mAbs specific for the human MHC molecules have been shown to cross-react with MHC molecules from humans, Old World primates, and New World primates (see Table 1), there has also been an extensive analysis of MHC molecules from these species at the nucleotide sequence level. Such analyses allow for more detailed comparisons of the conservation of the functions of these molecules than mAbs. Similarly, cloning and sequencing of the TCR genes in nonhuman primates has revealed a striking similarity among the various TCR genes of primates.

While MHC class II genes are well conserved between humans, Old World primates, and even in some cases New World primates, the MHC class I genes appear to have undergone many more changes. The MHC class I loci can be separated into classical or nonclassical loci. Classical MHC class I molecules, such as the human leukocyte antigen (HI.A)-A, -B and -C molecules, are highly polymorphic and their role in binding and presenting peptides is well established. The non-classical molecules from the HI.A-E, -E, and -G loci, for which specific functions have not, as yet been described, are more limited in their polymorphism. The HLA-J and -H loci, however, represent inactivated MHC class I loci or pseudogenes.

Nonhuman primates belonging to the Pongidae family are the most closely related species to humans. This family includes the common and pygmy chimpanzees (Pan troglodytes and Pan paniscus), gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus). Due to their close phylogenetic relationship to humans, chimpanzees express homologs of the HLA-A, -B, -C, -E, -F, -G, -H, and -J loci (Table 2 and Figure 1). An HLA-C homolog has also been identified in the gorilla, while no such homolog has been found in the orangutan, which suggests that the HLA-C locus likely arose through gene duplication after gorillas and orangutans last shared a common ancestor.

Analysis of the MHC class I genes from the rhesus monkey reveals that homologs of both the H1..A-A and -8 loci are present. Since rhesus monkeys last shared a common ancestor with humans approximately 35 million years ago, this indicates that the

Table 2 MHC class I and class II loci in human, great ape, Old World primate, and New World primate species


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