ROLE OF MHC CLASS I ALLELES IN VIRAL CONTROL OF SIV IN SOOTY MANGABEYS

MHC I 类等位基因在乌白眉猴 SIV 病毒控制中的作用

• 批准号: 8172408
• 负责人: Amitinder Kaur
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172408
• 关键词: Acquired Immunodeficiency Syndrome; Alleles; CD8-Positive T-Lymphocytes; Cercocebus atys; Complementary DNA; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; DNA; Exons; Funding; Genomics; Genotype; Grant; HIV; Institution; Length; MHC Class I Genes; Oligonucleotide Probes; Pathogenesis; Play; Primates; Research; Research Personnel; Resources; Role; SIV; Source; Study models; T-Lymphocyte Epitopes; United States National Institutes of Health; Viral; Virus Diseases; Virus Replication; base; cDNA Library; in vivo

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. MHC class I-restricted cytotoxic T-lymphocytes (CTL) play an important role in controlling human immunodeficiency virus and simian immunodeficiency virus (SIV) infection. As a natural host of SIV, sooty mangabeys (Cercocebus atys; Ceat) are a valuable model for the study of AIDS pathogenesis. We have previously defined several immunodominant SIV-specific CTL epitopes in sooty mangabeys and shown that CD8+ T lymphocytes inhibit SIV replication in vivo in naturally SIV-infected sooty mangabeys. In order to identify the MHC class I restriction of immunodominant CTL epitopes, we have cloned and characterized MHC class I genes of sooty mangabeys. cDNA libraries generated from two naturally SIV-infected sooty mangabeys were screened for MHC Class I cDNA with an oligonucleotide probe which hybridizes to a conserved region in exon 4 of primate MHC Class I genes. Based on a minimum of two clones with identical full-length MHC class I sequence, to date we have identified five MHC-A locus alleles designated as Ceat-A*0101 to Ceat-A*0501, and 12 MHC-B locus alleles designated as Ceat-B*0101 to Ceat-B*1201 in sooty mangabeys. Sequence specific primers (SSP) have been developed for the defined MHC class I alleles to enable large-scale MHC Class I typing of sooty mangabey genomic DNA by PCR-SSP. MHC genotyping of the colony of SIV-infected and SIV-negative sooty mangabeys at YNPRC is in progress.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 MHC I 类限制性细胞毒性 T 淋巴细胞 (CTL) 在控制人类免疫缺陷病毒和猿猴免疫缺陷病毒 (SIV) 感染中发挥重要作用。作为SIV的天然宿主，乌白眉猴（Cercocebus atys；Ceat）是研究艾滋病发病机制的一个有价值的模型。 我们之前已经在乌白眉猴中定义了几种免疫显性的 SIV 特异性 CTL 表位，并表明 CD8+ T 淋巴细胞在自然感染 SIV 的乌白眉猴体内抑制 SIV 复制。为了鉴定免疫显性 CTL 表位的 MHC I 类限制，我们克隆并表征了乌白眉猴的 MHC I 类基因。 使用与灵长类 MHC I 类基因外显子 4 中的保守区域杂交的寡核苷酸探针，对从两只天然 SIV 感染的乌白白眉猴生成的 cDNA 文库中筛选 MHC I 类 cDNA。 基于至少两个具有相同全长 MHC I 类序列的克隆，迄今为止，我们已经鉴定了 5 个 MHC-A 基因座等位基因，指定为 Ceat-A*0101 至 Ceat-A*0501，以及 12 个 MHC-B 基因座等位基因，指定为 Ceat-A*0101 至 Ceat-A*0501如乌白白眉猴中的 Ceat-B*0101 至 Ceat-B*1201。 已针对定义的 MHC I 类等位基因开发了序列特异性引物 (SSP)，以便能够通过 PCR-SSP 对乌白白眉基因组 DNA 进行大规模 MHC I 类分型。 YNPRC 正在对 SIV 感染和 SIV 阴性的乌白眉猴群体进行 MHC 基因分型。