Immunogenetics of Macaques Used for Biodefense and AIDS Research

用于生物防御和艾滋病研究的猕猴免疫遗传学

• 批准号: 8502384
• 负责人: David H. O'Connor
• 金额: $ 52.73万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8502384
• 关键词: AIDS vaccine development; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Alleles; Animal Model; Animals; Base Sequence; Binding; Biochemistry; CD8B1 gene; Cellular Immunity; Chinese People; Communicable Diseases; DNA Sequence; Data; Development; Disease; Disease Resistance; Family suidae; Filipino; Funding; Genbank; Genes; Genetic; Genetic Variation; Genotype; Grant; HIV; HIV-1; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Immunogenetics; Individual; Infection; Infectious Diseases Research; Laboratories; Lead; Length; Letters; Macaca; Macaca mulatta; Major Histocompatibility Complex; Methods; Modeling; Monkeys; Monoclonal Antibody R24; Natural Killer Cells; Oceans; Pathogenesis; Peptides; Population; Predisposition; Principal Investigator; Qualifying; Receptor Gene; Research; Research Personnel; Resources; SIV; T cell response; T-Lymphocyte Epitopes; T-Lymphocyte and Natural Killer Cell; Tail; Testing; Transcript; United States; Vaccines; biodefense; cost; deep sequencing; experience; immunoglobulin receptor; next generation; novel; pathogen; peptide I; prophylactic; public health relevance; pyrosequencing; receptor; response; southeast Asian

DESCRIPTION (provided by applicant): 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 and biodefense, a comprehensive understanding of major histocompatibility complex (MHC) and killer immunoglobulin receptor (KIR) genetics is required. In the initial project period of this grant, 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: Specific Aim 1, in which commonly expressed MHC class I and II alleles will be sequenced from cynomolgus, Chinese rhesus, and pig-tailed macaques. Specific Aim 2, in which full length KIR alleles will be sequenced from the same populations of macaques. Specific Aim 3, in which 8 MHC class I and 8 MHC class II peptide binding motifs will be determined. These Aims will take advantage of recent developments in high-throughput 'next generation' DNA sequencing to rapidly characterize full-length MHC and KIR alleles. At least 300 heretofore novel MHC class 1,150 MHC class II, and 300 KIR sequences will be identified. The experience of the investigative team in macaque immunogenetics, deep sequencing, and MHC biochemistry uniquely qualifies them to continue this important research.

描述（申请人提供）：猕猴是艾滋病疫苗开发最重要的动物模型，越来越多地用于生物防御研究。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。印度恒河猴具有最彻底的免疫遗传学特征;然而，其研究的可用性非常有限。中国猕猴、食蟹猴和猪尾猕猴越来越多地被用来缓解印度猕猴的短缺。随着对这些猕猴的研究变得越来越普遍，有一种新的认识认为，它们可能在特定研究中比印度恒河猴具有令人信服的优势。为了研究艾滋病病毒的细胞免疫和生物防御，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）遗传学。在该资助的初始项目期间，对来自不同来源的食蟹猴的MHC I类和II类等位基因进行了测序，并确定了食蟹猴中的第一个MHC肽结合基序。在这次更新中，我们将继续并扩大该项目，完成：具体目标1，其中通常表达的MHC I类和II类等位基因将从食蟹猴，中国恒河猴和猪尾猕猴测序。具体目标2，其中将对来自相同猕猴群体的全长KIR等位基因进行测序。特定目标3，其中将确定8个MHC I类和8个MHC II类肽结合基序。这些目标将利用高通量“下一代”DNA测序的最新发展，快速表征全长MHC和KIR等位基因。将鉴定至少300个迄今为止新的MHC 1类、150个MHC II类和300个KIR序列。研究团队在猕猴免疫遗传学、深度测序和MHC生物化学方面的经验使他们有资格继续这项重要的研究。