Characterization of MHC class I alleles in sooty mangabeys as a tool for evaluating cellular immunity in natural hosts of SIV infection

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 Nef20–28 CTL epitope. Ceat-B*1201/Nef20–28 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.

Convergent Evolution of HLA-C Downmodulation in HIV-1 and HIV-2

“…Similarly, Vpus from SIVgsn, SIVmus, and SIVden were also able to decrease HLA-C levels in infected cells, suggesting an ancient origin of this activity. This finding is surprising since HLA-C has been reported to be an evolutionarily rather young MHC-I molecule that can be found only in orangutans, chimpanzees, bonobos, gorillas, and humans but not in Old World monkeys such as the natural hosts of SIVgsn, SIVmus, or SIVden ( 69 – 72 ). This raises the possibility that the observed phenotype is not the result of a direct interaction of Vpu with HLA-C but involves a more indirect effect.…”

Association of erythrocyte sedimentation rate and C-reactive protein and clinical findings with HLA-DQ8 allele in Rheumatoid Arthritis patients

“…Human leukocyte antigen (HLA) system could be involved in RA incident through certain HLA alleles [14][15][16]. Recently numbers of MHC allele subtypes are identified by polymerase chain reaction (PCR) method [17].…”

TE-domestication and horizontal transfer in a putative Nef-AP1mu mimic of HLA-A cytoplasmic domain re-trafficking

“…[22][23][24][25] It is possible, of course, that the two footprints were separated in evolutionary time, with the 3 0 -tigger footprint resulting from a gene conversion involving the nascent SH3-MHC gene, e.g., via an ABL kinase exchange with a GTPaselike gene harboring the nascent NefL structures. [26][27][28] Finally, the inherent resistance of C. atys to SIV disease, [29][30][31] suggests that some biology linked to the Loc-105576907 orf might afford novel explanations, and quite possibly novel approaches to HIV-1 therapeutics. The T. syrichta Loc-103275158 orf is (as we have discussed) one such piece of biology.…”