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Summary Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi‐gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well‐defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi‐gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species’ immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.

In this document, we report the detection of 37 DRA alleles in macaque cohorts.

Chimpanzees experienced a reduction of the allelic repertoire at the major histocompatibility complex (MHC) class I A and B loci, which may have been caused by a retrovirus belonging to the simian immunodeficiency virus (SIV) family. Extended MHC haplotypes were defined in a pedigreed chimpanzee colony. Comparison of genetic variation at microsatellite markers mapping inside and outside the Mhc region was carried out in humans and chimpanzees to investigate the genomic extent of the repertoire reduction. Multilocus demographic analyses underscored that chimpanzees indeed experienced a selective sweep that mainly targeted the chromosomal segment carrying the Mhc class I region. Probably due to genetic linkage, the sweep also affected other polymorphic loci, mapping in the close vicinity of the Mhc class I region genes. Nevertheless, although the allelic repertoire at particular Mhc class I and II loci appears to be limited, naturally occurring recombination events allowed the establishment of haplotype diversity after the sweep. However, recombination did not have sufficient time to erase the signal of the selective sweep.

Here we report 51 novel major histocompatibility complex (MHC) class II alleles in a group of related olive baboons.

Summary: 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.

The Biomedical Primate Research Centre (BPRC) rhesus macaque colony was started with a large number of wild-caught animals originating mainly from the Indian subcontinent. The contemporary self-sustaining colony comprises approximately 800 individuals. We screened a large section of the colony for Mamu-DRB polymorphisms by applying the denaturing gradient gel electrophoresis (DGGE) technique. Based on disparate DGGE profiles, animals were selected for nucleotide sequence analysis. This approach allowed the detection of 25 unreported Mamu-DRB alleles, bringing to 126 the total number of alleles documented in the literature. This communication demonstrates that rhesus macaques, like humans, display extensive allelic polymorphism at the DRB region. Phylogenetic analyses illustrate that humans and rhesus macaques share several Mhc-DRB loci and lineages. Identical exon 2 sequences, however, which are shared between humans and rhesus macaques, were not observed. This indicates that most primate Mhc-DRB alleles are of post-speciation origin.

In the past decade, the major histocompatibility complex (MHC) class II region of several primate species has been investigated extensively. Here we will discuss the similarities and differences found in the MHC class II repertoires of primate species including humans, chimpanzees, rhesus macaques, cotton-top tamarins and common marmosets. Such types of comparisons shed light on the evolutionary stability of MHC class II alleles, lineages and loci as well as on the evolutionary origin and biological significance of haplotype configurations.

This study describes the characterization of a serological HLA-DQ"blank" specificity that segregates with the HLA-A2, -B7, -DR14, -DR52 haplotype. Although conventional serological typing techniques could not detect an HLA-DQ product on the haplotype positive for the HLA-DQ"blank" specificity, sequence-specific oligonucleotide (SSO) dot-blot analysis demonstrated the presence of the HLA-DQA1*01 and HLA-DQB1*05 alleles. Full-length cDNA nucleotide sequence analysis revealed that the HLA-DQB1 allele that segregated with the HLA-DQ"blank" specificity was identical to HLA-DQB1*05031. As for the HLA DQA1 allele, one nucleotide substitution distinguished the HLA-DQA1 "blank" allele from HLA-DQA1*0104. In exon 2 at nucleotide position 304 a C was substituted for a T (Arg-->Cys). Pending official recognition by the WHO Nomenclature Committee, this HLA-DQA1 "blank" allele is termed HLA-DQA1*"LA". Furthermore, it is postulated that the introduction of cysteine at amino acid position 102 abrogates the classical HLA-DQ1 specificity.

By the use of restriction fragment length polymorphism analysis 10 Taq I fragments could be identified for the MhcMamu-DQA1 region. A strong correlation exists between the occurrence of Mamu-DQA1/Taq I fragments and Mamu-DQA1 allelic sequence variation. Most restriction fragments correspond with a unique Mamu-DQA1 allele, with one exception being the Taq I 4.5 kb fragment that is associated with two Mamu-DQA1 alleles. The RFLP technique allowed the identification of 15 Mamu-DQB1/Taq I restriction fragments, whereas sequence analysis has permitted the characterization of at least 20 different Mamu-DQB1 alleles. In this communication two unpublished Mamu-DQB1 sequences are described. For Mamu-DQB1, on only four occasions was it possible to demonstrate a correlation between a certain fragment and an allelic sequence. These analyses, performed on material from truly homozygous animals, allowed us to define which combinations of Mamu-DQA1 and -DQB1 molecules form heterodimers at the cell surface. In addition, these studies are helpful in typing non-human primate species that are used in biomedical research.