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Discovery of gorilla MHC-C expressing C1 ligand for KIR (advance online)

MPG-Autoren
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Hans,  Jörg B.
Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Vigilant,  Linda
Molecular Genetics Laboratory, Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Hans_Discovery_Immunogen_2017.pdf
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Zitation

Hans, J. B., & Vigilant, L. (2017). Discovery of gorilla MHC-C expressing C1 ligand for KIR (advance online). Immunogenetics. doi:10.1007/s00251-017-1038-y.


Zitierlink: https://hdl.handle.net/21.11116/0000-0000-E7CA-8
Zusammenfassung
In comparison to humans and chimpanzees, gorillas show low diversity at MHC class I genes (Gogo), as reflected by an overall reduced level of allelic variation as well as the absence of a functionally important sequence motif that interacts with killer cell immunoglobulin-like receptors (KIR). Here, we use recently generated large-scale genomic sequence data for a reassessment of allelic diversity at Gogo-C, the gorilla orthologue of HLA-C. Through the combination of long-range amplifications and long-read sequencing technology, we obtained, among the 35 gorillas reanalyzed, three novel full-length genomic sequences including a coding region sequence that has not been previously described. The newly identified Gogo-C*03:01 allele has a divergent recombinant structure that sets it apart from other Gogo-C alleles. Domain-by-domain phylogenetic analysis shows that Gogo-C*03:01 has segments in common with Gogo-B*07, the additional B-like gene that is present on some gorilla MHC haplotypes. Identified in ~ 50% of the gorillas analyzed, the Gogo-C*03:01 allele exclusively encodes the C1 epitope among Gogo-C allotypes, indicating its important function in controlling natural killer cell (NK cell) responses via KIR. We further explored the hypothesis whether gorillas experienced a selective sweep which may have resulted in a general reduction of the gorilla MHC class I repertoire. Our results provide little support for a selective sweep but rather suggest that the overall low Gogo class I diversity can be best explained by drastic demographic changes gorillas experienced in the ancient and recent past.