title: CD8+ T-cell responses to different HIV proteins have discordant associations with viral load.
abstract: Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4013, South Africa.
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Kholiswa
authors.initials: K
authors.lastname: Ngumbela
authors.forename: Christina
authors.initials: C
authors.lastname: Thobakgale
authors.forename: Dhanwanthie
authors.initials: D
authors.lastname: Ramduth
authors.forename: Isobella
authors.initials: I
authors.lastname: Honeyborne
authors.forename: Eshia
authors.initials: E
authors.lastname: Moodley
authors.forename: Shabashini
authors.initials: S
authors.lastname: Reddy
authors.forename: Chantal
authors.initials: C
authors.lastname: de Pierres
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.forename: Nompumelelo
authors.initials: N
authors.lastname: Mkhwanazi
authors.forename: Karen
authors.initials: K
authors.lastname: Bishop
authors.forename: Mary
authors.initials: M
authors.lastname: van der Stok
authors.forename: Kriebashnie
authors.initials: K
authors.lastname: Nair
authors.forename: Nasreen
authors.initials: N
authors.lastname: Khan
authors.forename: Hayley
authors.initials: H
authors.lastname: Crawford
authors.forename: Rebecca
authors.initials: R
authors.lastname: Payne
authors.forename: Alasdair
authors.initials: A
authors.lastname: Leslie
authors.forename: Julia
authors.initials: J
authors.lastname: Prado
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: John
authors.initials: J
authors.lastname: Frater
authors.forename: Noel
authors.initials: N
authors.lastname: McCarthy
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: David
authors.initials: D
authors.lastname: Nickle
authors.forename: Christine
authors.initials: C
authors.lastname: Rousseau
authors.forename: Hoosen
authors.initials: H
authors.lastname: Coovadia
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D013019:South Africa; D019562:Viral Load; D014764:Viral Proteins / Q000378:metabolism*; D014766:Viremia / Q000276:immunology / Q000378:metabolism
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D006680:HLA Antigens; D014764:Viral Proteins