?The goals of the NHP MHC Gene Discovery and Typing Development Program are to advance the detailed knowledge base of nonhuman primate (NHP) major histocompatibility complex (MHC) genetic loci, alleles, and haplotypes, and their frequencies; expand discovery and characterization of NHP killer-cell immunoglobulin-like receptors (KIRs) genes, alleles, haplotypes, and frequencies; and develop robust, high-throughput genotyping and haplotyping methods.? Host genomics, and particularly major histocompatibility complex (MHC) class I genetics, are extremely important for maximizing the reproducibility and experimental robustness of nonhuman primate HIV/SIV vaccine studies. Because HIV cure strategies under development have different mechanisms of action, a targeted approach akin to MHC genotyping macaques in vaccine trials will likely be insufficient. Instead, genotyping of the MHC and other immune loci will need to be married with studies of high impact variation throughout the genome. The overarching goal of this research is to develop technologies that will enable simultaneous immunogenotyping and identification of protein-truncating variants in non-immune genes to support HIV cure studies in macaques. This project will develop and improve target-capture arrays that enable simultaneous exome sequencing and immunogenotyping (genomic profiling) of MHC class I and class II and killer immunoglobulin-like receptor (KIR) loci from NHP used in HIV cure research; stimulate community enthusiasm for utilizing macaque genomics in HIV cure studies; and improve macaque reference genomes by defining alternate sequence representations of MHC and KIR regions.
