title: Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses.
abstract: BACKGROUND
  The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined.
  
  
  METHODS
  HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence.
  
  
  RESULTS
  The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus-specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non-Gag proteins were the main target (P=.007).
  
  
  CONCLUSIONS
  Gag-specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. ramduthd1@ukzn.ac.za
authors.forename: Danni
authors.initials: D
authors.lastname: Ramduth
authors.forename: Polan
authors.initials: P
authors.lastname: Chetty
authors.forename: Nolwandle Cyloria
authors.initials: NC
authors.lastname: Mngquandaniso
authors.forename: Nonhlanhla
authors.initials: N
authors.lastname: Nene
authors.forename: Jason Davis
authors.initials: JD
authors.lastname: Harlow
authors.forename: Isobella
authors.initials: I
authors.lastname: Honeyborne
authors.forename: Nelisiwe
authors.initials: N
authors.lastname: Ntumba
authors.forename: Sharika
authors.initials: S
authors.lastname: Gappoo
authors.forename: Chiara
authors.initials: C
authors.lastname: Henry
authors.forename: Prakash
authors.initials: P
authors.lastname: Jeena
authors.forename: Marylyn Martina
authors.initials: MM
authors.lastname: Addo
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Cheryl
authors.initials: C
authors.lastname: Day
authors.forename: Hoosen
authors.initials: H
authors.lastname: Coovadia
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Philip
authors.initials: P
authors.lastname: Goulder
authors.forename: Bruce
authors.initials: B
authors.lastname: Walker
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D020543:Proteome / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D015683:Gene Products, gag; D020543:Proteome; D014764:Viral Proteins