IMMUNOGENETICS OF MACAQUES USED FOR BIODEFENSE AND AIDS RESEARCH

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：全面了解主要组织相容性复合体(MHC)和杀伤细胞免疫球蛋白受体(KIR)的遗传学，以研究细胞免疫对艾滋病病毒、生物恐怖威胁和生物防御的影响。 猕猴是艾滋病疫苗研发中最重要的动物模型，越来越多地被用于生物防御研究。一个人的免疫遗传学可以深刻地影响对艾滋病病毒和其他病原体的易感性。印度猕猴具有最彻底的免疫遗传学特征；然而，它们用于研究的可能性极其有限。为了缓解印度猕猴的短缺，越来越多的人依赖中国血统的恒河猴、食蟹猴和猪尾恒河猴。随着对这些猕猴的研究变得越来越普遍，有一种新的认识到，在特定的研究中，它们可能比印度起源的恒河猴具有令人信服的优势。为了研究对艾滋病病毒、生物恐怖威胁的细胞免疫和生物防御研究，需要全面了解主要组织相容性复合体(MHC)和杀伤免疫球蛋白受体(KIR)的遗传学。此前，对不同来源食蟹猴的MHC I、II类等位基因进行了测序，并确定了食蟹猴的第一个MHC多肽结合基序。在这次更新中，我们将通过完成三个具体目标来继续和扩大这个项目。在特定目标1中，将对食蟹猴、中国恒河猴和猪尾猕猴共同表达的MHC I和II类等位基因进行测序。我们将确定至少300个新的I类等位基因和150个新的II类等位基因的完整核苷酸序列。特定目标2将定义从相同种群的猕猴中测序的全长KIR等位基因。我们将识别至少300个新的KIR等位基因。在特定目标3中，我们将表征在特定目标1中确定的8个常见MHC I类和8个常见MHC II类异二聚体的肽结合基序。本研究使用了WNPRC动物服务、免疫学和病毒学服务、研究计算和遗传学服务。

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.