Limited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.

TitleLimited immunogenicity of HIV CD8+ T-cell epitopes in acute Clade C virus infection.
Publication TypeJournal Article
Year of Publication2011
AuthorsRadebe M, Nair K, Chonco F, Bishop K, Wright JK, van der Stok M, Bassett IV, Mncube Z, Altfeld M, Walker BD, Ndung'u T
JournalJ Infect Dis
Volume204
Issue5
Pagination768-76
Date Published09/2011
ISSN1537-6613
KeywordsAcute 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
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.

DOI10.1093/infdis/jir394
Alternate JournalJ. Infect. Dis.
PubMed ID21844303
PubMed Central IDPMC3156105
Grant ListK23 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
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