NHP MHC COMPLEX ALLELE DISCOVERY AND TYPING TECHNOLOGY DEVELOPMENT - HIV/AIDS

“NHP MHC基因发现和分型开发计划的目标是推进非人灵长类动物（NHP）主要组织相容性复合体（MHC）遗传基因座、等位基因和单倍型及其频率的详细知识基础;扩大NHP免疫细胞免疫球蛋白样受体（KIR）基因、等位基因、单倍型和频率的发现和表征;并开发出强大的、高通量的基因分型和单体型分型方法。” 目前，印度恒河猴是研究各种人类健康问题的最广泛使用的模型之一，从疾病和障碍到潜在的治疗和预防策略。它是目前HIV疫苗试验的最佳动物模型，最近RhCMV/SIV疫苗接种策略的成功提供了一个最令人信服的例子。由于对SIV的细胞介导的免疫应答对于这种（和其他）疫苗保护显然是至关重要的，因此对猕猴免疫应答遗传学的完整了解对于将动物模型的结果转化为人类是必不可少的。该项目将从俄勒冈州健康与科学大学疫苗和基因治疗研究所测试的猕猴SIV疫苗试验队列中的恒河猴的MHC I类和II类区域以及KIR中建立定相基因组序列;并从3种猕猴中的Fc γ受体（FCGR）基因复合物中建立定相基因组序列。

“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.” Currently the Indian rhesus macaque is one of the most widely used models for studying a variety of human health issues, ranging from diseases and disorders to potential therapies and preventive strategies. It is currently the best animal model for HIV vaccine testing, with the recent success of the RhCMV/SIV vaccination strategy contributing a most convincing example. Since cell-mediated immune responses to SIV are apparently crucial for this (and other) vaccine protection, a complete knowledge of the genetics of the immune response in macaques is essential for translation of results from the animal model to humans. This project will establish phased genomic sequences from the MHC class I and II regions and from KIR for rhesus macaques from the macaque SIV vaccine trial cohort tested at the Vaccine and Gene Therapy Institute at the Oregon Health & Sciences University; and establish phased genomic sequences from the Fc gamma receptor (FCGR) gene complex in 3 macaque species.