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

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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.