The immune and reproductive functions of human Natural Killer (NK) cells are regulated by interactions of the C1 and C2 epitopes of HLA-C with C1-specific and C2-specific lineage III killer cell immunoglobulin-like receptors (KIR). This rapidly evolving and diverse system of ligands and receptors is restricted to humans and great apes. In this context, the orangutan has particular relevance because it represents an evolutionary intermediate, one having the C1 epitope and corresponding KIR, but lacking the C2 epitope. Through a combination of direct sequencing, KIR genotyping and data mining from the Great Ape Genome Project (GAGP) we characterized the KIR alleles and haplotypes for panels of ten Bornean orangutans and 19 Sumatran orangutans. The orangutan KIR haplotypes have between five and ten KIR genes. The seven orangutan lineage III KIR genes all locate to the centromeric region of the KIR locus, whereas their human counterparts also populate the telomeric region. One lineage III KIR gene is Bornean-specific, one is Sumatran-specific and five are shared. Of twelve KIR gene-content haplotypes five are Bornean-specific, five are Sumatran-specific and two are shared. The haplotypes have different combinations of genes encoding activating and inhibitory C1 receptors that can be of higher or lower affinity. All haplotypes encode an inhibitory C1 receptor, but only some haplotypes encode an activating C1 receptor. Of 130 KIR alleles, 55 are Bornean-specific, 65 are Sumatran specific and ten are shared.

The ancestral progenitor of common chimpanzees and bonobos experienced a selective sweep that ravaged its major histocompatibility complex (MHC) class I repertoire. The causative agent was probably an ancestral retrovirus, highly related to the contemporary HIV-1 strain, which initiated the acquired immunodeficiency syndrome pandemic in the human population. As a direct result, MHC class I allotypes with the capability of targeting conserved retroviral elements were enriched in the ancestral progenitor. Even today, the impact can be traced back by studying the functional capacities of the contemporary MHC class I allotypes of common chimpanzees. Viruses, however, have developed several strategies to manipulate the cell-surface expression of MHC class I genes. Monitoring the presence and absence of the MHC class I allotypes on the cell surface is conducted, for instance, by the hosts' gene products of the killer cell immunoglobulin-like receptor (KIR) complex. Hence, one may wonder whether-in the future-any clues with regard to the signature of the MHC class I selective sweep might be unearthed for the KIR genes as well.

Rhesus macaques (Macaca mulatta) mainly originating from India were analysed for their major histocompatibility complex class I-related (MIC) gene repertoire. Thus far, three distinct genes, designated MIC1, MIC2 and MIC3, have been identified in the rhesus macaque. In addition, an MICD pseudogene has been described mapping apart from the other loci in a telomeric direction. Genomic comparisons and the presence of a characteristic microsatellite in exon 5 suggest that the MIC1 gene is the equivalent of the human MICA gene. Hence, the MIC2 gene, lacking the microsatellite - as do humans -, is considered to be the equivalent of human MICB. The MIC3 gene, a hybrid of MICA and MICB, seems to be generated by a crossing-over event with one breakpoint in intron 3 and accordingly is named MICA/B. Apart from their human counterparts, MICA, MICB and MICA/B cluster in separate branches in the phylogenetic tree, confirming the hybrid character of the MICA/B gene. Population analyses have shown that the various genes display polymorphism, and six MICA, five MICB and three MICA/B alleles have been identified. In the panel of homozygous typing cells, two distinct haplotype configurations have been defined by segregation analyses. Each haplotype comprises an MICB gene in conjunction with either an MICA or an MICA/B gene. Furthermore, the presence of a polymorphic microsatellite in the MICA and MICA/B alleles facilitates speedy and accurate haplotyping.