Unparalleled complexity of the MHC class I region in rhesus macaques

Abstract

The highly polymorphic gene products of the classical MHC class I genes in humans (HLA-A, HLA-B, and HLA-C) play a critical role in the immune defense against intracellular infections. Because non-human primates are important models for AIDS vaccine research, rhesus monkeys from a thoroughly pedigreed and serotyped colony were subjected to full-length cDNA analysis of MHC class I gene transcripts. Rhesus macaques express multiple dominant Mamu-A and Mamu-B transcripts (majors) per chromosome, which are characterized by high expression levels. The presence of additional cDNAs with low levels of expression (minors) suggests evidence for transcriptional control of MHC class I genes. Moreover, phylogenetic analyses illustrate that most of the Mamu-A and Mamu-B loci/lineages identified display no or only limited levels of allelic polymorphism. Thus, MHC class I diversity in rhesus macaques is typified by the existence of an unmatched high number of Mamu-A and Mamu-B region configurations that exhibit polymorphism with regard to the number and combination of transcribed loci present per chromosome.

Fig. 1.

Segregation of serotypes and Mamu-A and Mamu-B cDNAs in a Mendelian fashion in a rhesus macaque family. The maternal and paternal chromosomes are designated p–u. Serotypes are shown in brackets, and cDNAs are depicted in italics.

Fig. 2.

Phylogenetic tree of full-length Mamu-A sequences. The tree was constructed according to the neighbor-joining method, and bootstrap values based on 1,000 replications are indicated.

Fig. 3.

Phylogenetic tree of full-length Mamu-B cDNAs. The tree was constructed according to the neighbor-joining method, and bootstrap values based on 1,000 replications are indicated. Serotypes have been provided.

Fig. 4.

Schematic representation of nine Mamu-B region configurations. The physical order and distance of the genes responsible for the major cDNA transcripts have not yet been defined. Vertical alignment of cDNAs reflects identical locus designation at the genomic level.