|Title||Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Radebe M, Nair K, Chonco F, Bishop K, Wright JK, van der Stok M, Bassett IV, Mncube Z, Altfeld M, Walker BD, Ndung'u T|
|Journal||J Infect Dis|
|Keywords||Acute Disease, CD8-Positive T-Lymphocytes, Enzyme-Linked Immunospot Assay, Epitopes, T-Lymphocyte, Gene Products, gag, Gene Products, nef, HIV Infections, HIV Seropositivity, HIV-1, Humans, Interferon-gamma, RNA, Viral, Time Factors, Viral Load|
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.
|Alternate Journal||J. Infect. Dis.|
|PubMed Central ID||PMC3156105|
|Grant List||K23 AI 068458 / AI / NIAID NIH HHS / United States |
K23 AI068458 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R01 MH090326 / MH / NIMH NIH HHS / United States
R01-AI067073 / AI / NIAID NIH HHS / United States
R37 AI067073 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.