AIDS in chimpanzees: the role of MHC genes.

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.

Two Orangutan Species Have Evolved Different KIR Alleles and Haplotypes.

The immune and reproductive functions of human 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 Ig-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, we characterized the KIR alleles and haplotypes for panels of 10 Bornean orangutans and 19 Sumatran orangutans. The orangutan KIR haplotypes have between 5 and 10 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 12 KIR gene-content haplotypes, 5 are Bornean specific, 5 are Sumatran specific, and 2 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 10 are shared.