Limited Immunogenicity of HIV CD8+ T-Cell Epitopes in Acute Clade C Virus Infection
| Autor: | Marcus Altfeld, Jaclyn K. Wright, Fundisiwe Chonco, Kriebashnie Nair, Karen S. Bishop, Mary van der Stok, Zenele Mncube, Mopo Radebe, Ingrid V. Bassett, Bruce D. Walker, Thumbi Ndung'u |
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| Rok vydání: | 2011 |
| Předmět: |
Enzyme-Linked Immunospot Assay
Time Factors Epitopes T-Lymphocyte Gene Products gag HIV Infections Viremia Immunodominance CD8-Positive T-Lymphocytes Biology Gene Products nef Virus Epitope Interferon-gamma Major Articles and Brief Reports Immune system HIV Seropositivity medicine Humans Immunology and Allergy Immunogenicity virus diseases Viral Load medicine.disease Virology CTL Infectious Diseases Acute Disease Immunology HIV-1 RNA Viral Viral load |
| Zdroj: | The Journal of Infectious Diseases. 204:768-776 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jir394 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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