Limited Immunogenicity of HIV CD8⁺ T-Cell Epitopes in Acute Clade C Virus Infection

• Published in: The Journal of infectious diseases Vol. 204; no. 5; pp. 768 - 776
• Main Authors: Radebe, Mopo, Nair, Kriebashnie, Chonco, Fundisiwe, Bishop, Karen, Wright, Jaclyn K., van der Stok, Mary, Basse, Ingrid V., Mncube, Zenele, Altfeld, Marcus, Walker, Bruce D., Ndung'u, Thumbi
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2011
• Subjects: Acute Disease; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Enzyme-Linked Immunospot Assay; Epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; Gene Products, gag - immunology; Gene Products, nef - immunology; HIV; HIV 1; HIV infections; HIV Infections - immunology; HIV Seropositivity - immunology; HIV-1 - immunology; HIV/AIDS; HLA antigens; Humans; Infections; Infectious diseases; Interferon-gamma - blood; Major and Brief Reports; Medical sciences; Microbiology; Miscellaneous; RNA, Viral - blood; T lymphocytes; Time Factors; Viral Load; Viremia; Virology; Viruses; Virus; Infection; Antigenic determinant; Immunogenicity; Acute; Viral disease; Retroviridae; Human immunodeficiency virus; Lentivirus; CD8 T lymphocyte
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jir394

Background. Human immunodeficiency virus type 1 (HlV-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, antiretro viral-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 pep tides 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.