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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 MHC 1类限制性细胞毒性T淋巴细胞（CTL）在人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）感染中起重要作用。白眉猴（Cercocibusatys; Ceat）作为SIV的自然宿主，是研究艾滋病发病机制的重要动物模型。我们以前已经确定了几个免疫显性SIV特异性CTL表位在免疫白眉猴，并表明，CD*+T淋巴细胞抑制SIV复制在体内自然SIV感染白眉猴。为了鉴定免疫显性CTL表位的MHC 1类限制性，我们克隆并鉴定了MHC 1类基因。从两个自然SIV感染的白眉猴产生的cDNA文库中筛选的MHC 1类cDNA与寡核苷酸探针，杂交到一个保守区域。基于最少两个克隆具有相同的全长MHC 1类序列，迄今为止，我们已经确定了5个MCH：-A基因座等位基因，命名为Ceat-A*0101至Ceat-A*0501，和12个MHC-B基因座等位基因，命名为Ceat-B*0101至Ceat-B*1201。已针对所定义的MHC 1类等位基因开发了序列特异性引物（SSP），以使得能够通过PCR-SSP对大规模的白眉猴基因组DNA进行MHC 1类分型。在耶基斯，对SIV感染和SIV阴性的白眉猴的殖民地进行MHC基因分型的工作正在进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MHC class 1-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 (Cercocibus 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 CD*+T lymphocytes inhibit SIV replication in vivo in naturally SIV-infected mangabeys. In order to identify the MHC class 1 restriction of immunodominant CTL epitopes, we have cloned and characterized MHC class 1 genes. cDNA libraries generated from two naturally SIV-infected mangabeys were screened for MHC Class 1 cDNA with an oligonucleotide probe, which hybridizes to a conserved region. Based on a minimum of two clones with identical full-length MHC class 1 sequence, to date we have identified five MCH:-A locus alleles designated as Ceat-A*0101 to Ceat-A*0501, and 12 MHC-B locus alleles designated at Ceat-B*0101 to Ceat-B*1201 in sooty mangabeys. Sequence specific primers (SSP) have been developed for the defined MHC class 1 alleles to enable large-scale MHC Class 1 typing of sooty mangabey genomic DNA by PCR-SSP.. MHC genotyping of the colony of SIV-infected and SIV-negative sooty mangabeys at Yerkes is in progress.