title: Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.
abstract: Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.
authors.affiliation: Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. sarah.rowland-jones@ndm.ox.ac.uk
authors.forename: S L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: T
authors.initials: T
authors.lastname: Dong
authors.forename: K R
authors.initials: KR
authors.lastname: Fowke
authors.forename: J
authors.initials: J
authors.lastname: Kimani
authors.forename: P
authors.initials: P
authors.lastname: Krausa
authors.forename: H
authors.initials: H
authors.lastname: Newell
authors.forename: T
authors.initials: T
authors.lastname: Blanchard
authors.forename: K
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: J
authors.initials: J
authors.lastname: Oyugi
authors.forename: E
authors.initials: E
authors.lastname: Ngugi
authors.forename: J
authors.initials: J
authors.lastname: Bwayo
authors.forename: K S
authors.initials: KS
authors.lastname: MacDonald
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: F A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D000595:Amino Acid Sequence; D015331:Cohort Studies; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D016333:HIV Protease / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D059911:HLA-B18 Antigen; D006801:Humans; D007113:Immunity, Innate; D007630:Kenya; D010455:Peptides; D017421:Sequence Analysis; D011477:Sex Work; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D010455:Peptides; D054303:HIV Reverse Transcriptase; D016333:HIV Protease