title: Impact of APOBEC Mutations on CD8+ T Cell Recognition of HIV Epitopes Varies Depending on the Restricting HLA.
abstract: We previously showed that APOBEC-mediated mutations in HIV CD8 T-cell epitopes generally reduce recognition by CD8 T cells. Here, we examined this effect in the context of histocompatibility-linked leukocyte antigen (HLA) alleles differentially associated with disease progression rates. For HLA-B57-restricted epitopes, APOBEC mutations generally diminished CD8 T cell recognition. Conversely, recognition of HLA-B35-restricted epitopes was consistently enhanced. For epitopes that can be presented by either HLA-A2 or A3, the same APOBEC mutation had differential effects on CD8 T cell recognition, depending on the individual's HLA genotype. The pattern of HLA dependence provides additional evidence that APOBEC action is channeled toward cytotoxic CD8 T-cell escape.
authors.affiliation: Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Krista D
authors.initials: KD
authors.lastname: Squires
authors.forename: Mahdis
authors.initials: M
authors.lastname: Monajemi
authors.forename: Claire F
authors.initials: CF
authors.lastname: Woodworth
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.forename: Mani
authors.initials: M
authors.lastname: Larijani
mesh_terms: D000071479:APOBEC-1 Deaminase; D018414:CD8-Positive T-Lymphocytes; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009154:Mutation
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase