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- Title
Characterization of MHC class I alleles in sooty mangabeys as a tool for evaluating cellular immunity in natural hosts of SIV infection.
- Authors
Wang, Zichun; Metcalf, Benjamin; Kasheta, Melissa; Kasala-Hallinan, Caitlin; Tran, Dollnovan; Johnson, R.; Else, James; Karl, Julie; O'Connor, David; Apetrei, Cristian; Kaur, Amitinder
- Abstract
Although immune pressure exerted by MHC class I-restricted cytotoxic T lymphocytes (CTL) are an important determinant of outcome in pathogenic HIV and SIV infection, lack of data on MHC class I genes has hampered study of its role in natural hosts with nonpathogenic SIV infection. In this study, we cloned and characterized full-length MHC class I genes derived from the cDNA library of two unrelated naturally infected sooty mangabeys ( Cercocebus atys) in whom SIV-specific CTL epitopes were previously mapped. Twenty one full-length MHC class I alleles consisting of five MHC-A (Ceat-A), 13 MHC-B (Ceat-B), and three MHC-E (Ceat-E) alleles were identified. Sequence-specific primers (SSP) for high-throughput screening of genomic DNA by PCR were developed for 16 of the 18 Ceat-A and Ceat-B alleles. Screening of 62 SIV-negative and 123 SIV-infected sooty mangabeys at the Yerkes National Primate Research Center (YNPRC) revealed the presence of up to four MHC-A and eight MHC-B alleles in individual mangabeys, indicating that similar to macaque species, mangabeys have at least two duplications of the MHC-A locus and four duplications of the MHC-B locus in the absence of an MHC-C locus. Using stable transfectants of Ceat MHC Class I alleles in the MHC-null 721.221 cell line, we identified Ceat-B*12:01 as the restricting allele of a previously reported Nef CTL epitope. Ceat-B*1201/Nef tetramers identified tetramer-positive CD8+ T lymphocytes in Ceat-B*1201-positive SIV-infected mangabeys. This study has laid the groundwork for comprehensive analysis of CTL and SIV evolution in a natural host of SIV infection.
- Subjects
MANGABEYS; MAJOR histocompatibility complex; ALLELES; CELLULAR immunity; SIMIAN immunodeficiency virus; CYTOTOXIC T lymphocyte-associated molecule-4
- Publication
Immunogenetics, 2015, Vol 67, Issue 8, p447
- ISSN
0093-7711
- Publication type
Article
- DOI
10.1007/s00251-015-0853-2