title: Differences in HIV-specific T cell responses between HIV-exposed and -unexposed HIV-seronegative individuals.
abstract: HIV-1-specific T lymphocyte responses in individuals exposed to HIV-1 but who remain persistently seronegative (HESNs) have been reported in some but not all previous studies. This study was designed to resolve unequivocally the question of whether HESNs make HIV-1-specific T cell responses. We performed a blind investigation to measure HIV-1-specific T cell responses in both HIV-1-serodiscordant couples and HIV-1-unexposed seronegative controls (HUSNs). We found low-frequency HIV-1-specific T cells in both HESNs and HUSNs but show that the response rates were higher over time in the former (P = 0.01). Furthermore, the magnitudes of the HIV-1-specific T cell responses were significantly higher among responding HESNs than among HUSNs over time (P = 0.002). In both groups, responses were mediated by CD4 T cells. The responses were mapped to single peptides, which often corresponded to epitopes restricted by multiple HLA-DR types that have previously been detected in HIV-1-infected patients. HIV-1-specific T cell responses in HUSNs and some HESNs likely represent cross-reactivity to self or foreign non-HIV-1 antigens. The significantly greater T cell responses in HESNs, including in two who were homozygous for CCR5Δ32, demonstrates that HIV-1-specific T cell responses can be induced or augmented by exposure to HIV-1 without infection.
authors.affiliation: The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS United Kingdom.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ritchie
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Campion
authors.forename: Jakub
authors.initials: J
authors.lastname: Kopycinski
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.forename: Z Maggie
authors.initials: ZM
authors.lastname: Wang
authors.forename: Kruti
authors.initials: K
authors.lastname: Pandya
authors.forename: Stephen
authors.initials: S
authors.lastname: Moore
authors.forename: Michael K P
authors.initials: MK
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Brackenridge
authors.forename: Kristin
authors.initials: K
authors.lastname: Kuldanek
authors.forename: Kenneth
authors.initials: K
authors.lastname: Legg
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Eric L
authors.initials: EL
authors.lastname: Delwart
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008297:Male
chemical_list: D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D006684:HLA-DR Antigens