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 HIV and 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, MHC class I alleles were characterized from a cDNA library in two naturally SIV-infected sooty mangabeys. Based on at least two clones of identical full-length MHC class I sequence being present per group, we have identified five MHC-A (Ceat-A*01 to Ceat-A*05) and twelve MHC-B (Ceat-B*01 to Ceat-B*12) class I alleles in sooty mangabeys. These data suggest that 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. Detailed phylogenetic characterization of the exon 2 and exon 3 nucleotides in one Ceat-A allele (Ceat-A*01) and six Ceat-B alleles (Ceat-B*01 to Ceat-B*06) has revealed that Ceat-A*01 clusters together with Mafa-A*07 and Mane-A*09 (95% nucleotide and 91% amino acid homology), while Ceat-B*01 clustered with Mamu-B*41 and Mamu-B*65 (94% nucleotide and 86% amino acid homology). Ceat-B*02, Ceat-B*04 and Ceat-B*06 clustered tightly together and shared almost 96% nucleotide and 91% amino acid homology with Pacy-B*03. Ceat-B*03 and Ceat-B*05 also clustered together (97% nucleotide and 95% amino acid homology) but did not show a greater than 91% nucleotide homology to any other primate MHC-B allele. Future identification of the MHC class I restriction of CTL epitopes presented by high frequency mangabey MHC class I alleles will facilitate study of the role of cellular immunity in maintaining nonpathogenic SIV infection in sooty mangabeys.
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