title: Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) responses contribute to the decline in acute peak viremia following infection. However, data on the relative immunogenicity of CD8(+) T-cell epitopes during and after acute viremia are lacking.
  
  
  METHODS
  We characterized CD8(+) T-cell responses in 20 acutely infected, antiretroviral-naive individuals with HIV-1 subtype C infection using the interferon-γ enzyme-linked immunosorbent spot assay. Eleven of these had not fully seroconverted at the time of analysis. Viruses from plasma were sequenced within defined cytotoxic T-lymphocyte (CTL) cell epitopes for selected subjects.
  
  
  RESULTS
  At approximately 28 days after estimated initial infection, CD8(+) T-cell responses were directed against an average of 3 of the 410 peptides tested (range, 0-6); 2 individuals had no detectable responses at this time. At 18 weeks, the average number of peptides targeted had increased to 5 (range 0-11). Of the 56 optimal Gag CTL epitopes sequenced, 31 were wild-type in the infecting viruses, but only 11 of 31 elicited measurable CD8(+) T-cell responses.
  
  
  CONCLUSIONS
  These data demonstrate that the majority of CD8(+) responses are not elicited during acute HIV infection despite the presence of the cognate epitope in the infecting strain. There is a need to define factors that influence lack of induction of effective immune responses and the parameters that dictate immunodominance in acute infection.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Mopo
authors.initials: M
authors.lastname: Radebe
authors.forename: Kriebashnie
authors.initials: K
authors.lastname: Nair
authors.forename: Fundisiwe
authors.initials: F
authors.lastname: Chonco
authors.forename: Karen
authors.initials: K
authors.lastname: Bishop
authors.forename: Jaclyn K
authors.initials: JK
authors.lastname: Wright
authors.forename: Mary
authors.initials: M
authors.lastname: van der Stok
authors.forename: Ingrid V
authors.initials: IV
authors.lastname: Bassett
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D000208:Acute Disease; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D012367:RNA, Viral / Q000097:blood*; D013997:Time Factors; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015693:Gene Products, nef; D012367:RNA, Viral; D007371:Interferon-gamma