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

Emory University, Atlanta GA

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Abstract

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 and are being used to MHC type the colony of SIV-infected and SIV-negative sooty mangabeys at YNPRC. To date, samples have been collected from 155 animals for processing.