This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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, we have identified five MHC-A locus alleles designated as Ceat-A*01 to Ceat-A*05, and 12 MHC-B locus alleles designated as Ceat-B*01 to Ceat-B*12. No MHC-C locus alleles were detected. One mangabey had one A-locus and six B-locus alleles, while the second mangabey had four A-locus and six B-locus alleles. Thus, sooty mangabeys are similar to other Old World primates in not having a MHC-C locus and in having one or more duplications of the MHC-A and B loci. Sequence specific primers (SSP) have been developed to enable large-scale MHC Class I typing of sooty mangabey genomic DNA by PCR-SSP. Two high frequency alleles; Ceat-A*04 and Ceat-B*12 detected in 41.9% and 35.5% of screened animals have been identified. Thus far, the MHC restriction of a previous defined CTL epitope in SIV Nef has been identified as Ceat-B*12. The identification of the MHC class I restriction of dominant SIV-specific CTL epitopes in sooty mangabeys will enable the use of tetramers to study the role of CTL in maintaining nonpathogenic SIV infection in sooty mangabeys.
Showing the most recent 10 out of 365 publications
