Abstract
The major histocompatibility complex (MHC) class I genes play a critical role within the immune system, both by the presentation of antigens from intracellular pathogens to immunocompetent cells and by the interaction with killer cell immunoglobulin-like receptors (KIR) on natural killer cells (NK cells). Genes of the MHC are highly diverse, and MHC variation can have effects on the immune functionality of individuals; hence, comparisons of MHC diversity among closely related phylogenetic taxa may give insight into the factors responsible for the shaping of its diversity. The four geographically separated chimpanzee subspecies differ in their overall genetic diversity, have different population histories, and are confronted with different pathogens in their natural habitat, all of which may affect MHC class I DNA sequence diversity. Here, we compare the MHC-B exon two DNA sequence diversity from 24 wild western and 46 wild eastern chimpanzees using necropsy and noninvasively collected fecal samples, respectively. We found a higher MHC-B exon two nucleotide diversity, in our western than eastern chimpanzees. The inclusion of previously published MHC-B exon two data from other western and eastern chimpanzees supported this finding. In addition, our results confirm and extend the finding of a very low C1 epitope frequency at eastern chimpanzee MHC-B molecules, which likely affects the ability of these molecules to interact with NK cells. While the understanding of the differing pathogen environments encountered by disparate populations of a species is a challenging endeavor, these findings highlight the potential for these pathogens to selectively shape immune system variation.
Highlights
The mammalian immune system is critically dependent on genes of the major histocompatibility complex (MHC), which encodes for cellular surface proteins responsible for the presentation of antigens to immunocompetent cells (Townsend and Bodmer 1989)
The PCR success rate was 80% (45 of 56) using DNAs derived from necropsy samples and 77% (94 of 112) for DNAs derived from feces
We found that for the two possible Bw4 and C1 (MHC-B-C1) killer cell immunoglobulin-like receptors (KIR) epitopes at the chimpanzee MHC-B locus, only our set of western chimpanzee sequences contained both the Bw4 and C1 epitopes, whereas our set of eastern chimpanzee sequences had only the Bw4 epitope (Tables 1 and 2; Fig. 6)
Summary
The mammalian immune system is critically dependent on genes of the major histocompatibility complex (MHC), which encodes for cellular surface proteins responsible for the presentation of antigens to immunocompetent cells (Townsend and Bodmer 1989). MHC class I molecules defend against intracellular pathogens by presenting antigens mostly derived from viral proteins or cancerinfected cells (reviewed in Rock et al 2016; Sommer 2005). Along with their role in antigen presentation to T cells, MHC class I molecules interact with killer cell. NK cell responses are the result of a balance of stimulating and inhibiting signals derived from cell surface receptors like KIRs (Lanier 2003). The NK cell responses substantially support the defense against viral infections by contributing to the innate immunity (Waggoner et al 2016; Wroblewski et al 2019)
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