Immunogenetics of Primates Used for Bioterror Research

描述（由申请人提供）： 非人灵长类动物在涉及A-C类病原体的研究中起着重要作用。食蟹猴（M. fascicularis）是特别理想的，因为它们相对便宜且可广泛获得。然而，对食蟹猴的免疫遗传学知之甚少，使病原体特异性细胞免疫应答的评价复杂化。 具体目标1：我们将确定食蟹猴表达的至少60种主要组织相容性复合体（MHC）I类和50种MHC II类分子，并开发这些等位基因的高通量基因分型方法。MHC I类和II类等位基因在来自不同国家的食蟹猴中可能有所不同，因此我们将研究来自中国、毛里求斯、越南、印度尼西亚和菲律宾的动物的免疫遗传学。2003财政年度，从这些国家进口的食蟹猴超过12 000只。 在特定目标2中，我们将为特定目标1中鉴定的10种常见MHC I类和10种常见MHC II类等位基因开发初步的肽结合基序。如果来自不同地区的食蟹猴具有不同的MHC等位基因库，我们将专注于在中国，越南和越南猕猴中发现的等位基因的肽结合基序的定义。在2003财政年度进口到美国的食蟹猴中，超过75%是从这些国家进口的。 经验丰富的分子免疫学家和蛋白质生物化学家的优势相结合，在这个建议，使食蟹猴主要组织相容性复合体（MHC）分子的高通量表征和病原体衍生的肽，结合到他们。这些研究将促进物种特异性试剂（如MHC：肽四聚体）的开发，从而扩大食蟹猴在临床前疫苗试验和疾病发病机制研究中的应用。

DESCRIPTION (provided by applicant): Nonhuman primates are instrumental in research involving Category A-C pathogens. Cynomolgus macaques (M. fascicularis) are particularly desirable because they are comparatively inexpensive and widely available. However, little is known about the immunogenetics of Cynomolgus macaques, complicating the evaluation of pathogen-specific cellular immune responses. In Specific Aim 1: We will 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 genotyping 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 Philippines. 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 10 common 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 alleles 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 immunologists and protein biochemists are 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 on preclinical vaccine trials and studies of disease pathogenesis.