This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To gain a comprehensive understanding of major histocompatibility complex (MHC) and killer immunoglobulin receptor (KIR) genetics, in order to study cellular immunity to AIDS viruses, bioterror threats and for biodefense research. Macaque monkeys are the most important animal model for AIDS vaccine development and are increasingly being used in biodefense research. An individual's immunogenetics can profoundly influence susceptibility to AIDS viruses and other pathogens. Indian-origin rhesus macaques have the most thoroughly characterized immunogenetics;however, their availability for research is extremely limited. Chinese-origin rhesus macaques, cynomolgus macaques, and pig-tailed macaques are increasingly relied upon to alleviate the shortage of Indian- rhesus macaques. As studies with these macaques become more common, there is a newfound appreciation that they may offer compelling advantages over Indian-origin rhesus macaques for specific studies. To study cellular immunity to AIDS viruses, bioterror threats and for biodefense research, a comprehensive understanding of major histocompatibility complex (MHC) and killer immunoglobulin receptor (KIR) genetics is required. Previously, MHC class I and II alleles were sequenced from cynomolgus macaques from different origins and the first MHC peptide binding motifs in cynomolgus macaques were determined. In this renewal, we will continue and expand this project by completing three specific aims.
In Specific Aim 1, commonly expressed MHC class I and II alleles will be sequenced from cynomolgus, Chinese rhesus, and pig-tailed macaques. We will determine the complete nucleotide sequences of at least 300 novel class I and 150 novel class II alleles.
Specific Aim 2 will define full length KIR alleles sequenced from the same populations of macaques. We will identify at least 300 novel KIR alleles.
In specific aim 3 we will characterize peptide binding motifs for eight common MHC class I and eight common MHC class II heterodimers identified in specific aim 1. This research used WNPRC Animal Services, Immunology &Virology Services, Research Computing and Genetics Services.
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