Immunogenetics of Primates Used for Bioterror Research

非人灵长类动物在涉及A-C类生物防御病原体的研究中起着重要作用。食蟹 猕猴（M. Fascicularis）是特别理想的，因为它们比较便宜且广泛应用于 available.然而，对食蟹猴的免疫遗传学知之甚少，这使得 病原体特异性细胞免疫应答的评价。 在具体目标1中：我们将确定至少60种主要组织相容性复合物（MHC）I类和50种 食蟹猴表达的MHC II类分子，并开发高通量基因工程方法。 这些等位基因没有分型。MHC I类和II类等位基因在获得的食蟹猴中可能不同。 所以我们将研究来自中国，毛里求斯，越南， 印度尼西亚和菲律宾。从这些国家进口的食蟹猴超过12，000只 2003财政年度。 在Specific Aim 2中，我们将开发10种常见的MHC I类和10种常见的MHC II类的初步肽结合基序。 在特异性目标1中鉴定的常见MHC II类等位基因。如果来自不同地区的食蟹猴 有不同的MHC等位基因库，我们将集中在肽结合基序的定义为等位基因发现 在中国、越南和越南猕猴中。进口食蟹猴超过75% 在2003财政年度进入美国的外国人都来自这些国家之一。 经验丰富的分子免疫遗传学家和蛋白质生物化学家的优势结合在一起， 建议，使食蟹猴主要组织相容性的高通量表征 MHC复合物分子和与它们结合的病原体衍生肽。这些研究将有助于 物种特异性试剂（如MHC：肽四聚体）的开发， 临床前疫苗试验和疾病发病机制研究中的食蟹猴。

Nonhuman primates are instrumental in research involving Category A-C biodefense pathogens. Cynomolgus macaques (M. Fascicularis) are particularly desireable because they are comparitively inexpensive and widely available. However, little is known about the immunogenetics ot Cynomolgus macaques, complicating the evaluation of pathogen-specific cellular immune responses. in Specific Aim 1: Wewill identify at least 60 Major Histocompatibility Complex (MHC) class I and 50 MHC class II molecules expressed by Cynomolgus macaques and develop methods for high-throughput ge- notyping for these alleles. MHC class I and class II alleles may vary among Cynomolgus macaques obtained from different countries, so we will examine the immunogenetics of animals from China, Mauritius, Vietnam, Indonesia, and the Phillipines. More than 12,000 Cynomolgus macaques were imported from these countries in FY2003. In Specific Aim 2, we will develop preliminary peptide binding motifs for 10common MHC class I and 10 common MHC class II alleles identified in Specific Aim 1. If Cynomolgus macaques from different regions have distinct MHC allele repertoires, we will focus on the definition of peptide binding motifs for alleies found in Chinese, Mauritian, and Vietnamese macaques. More than 75% of the Cynomolgus macaques imported into the United States in FY2003 were brought from one of these countries. The strengths of experienced molecular immunogeneticists and protein biochemists a-e combined in this proposal, enabling the high-throughput characterization of Cynomolgus macaque major histocompatibility complex (MHC) molecules and the pathogen-derived peptides that bind to them. These studies will facilitate the development of species-specific reagents (such as MHC: peptide tetramers) that expand the utility of Cynomolgus macaques in preclinical vaccine trials and studies of disease pathogenesis.