期刊
JOURNAL OF VIROLOGY
卷 91, 期 7, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02477-16
关键词
CD4 T helper cells; MHC class II tetramers; human immunodeficiency virus; HIV
类别
资金
- U.S. National Institutes of Health [R37 AI067073]
- South African Research Chairs Initiative of the South African Department of Science and Technology
- National Research Foundation (NRF)
- Victor Daitz Foundation
- Mark and Lisa Schwartz Foundation
- Bill and Melinda Gates Foundation
- International AIDS Vaccine Initiative (IAVI) [UKZNRSA1001]
- NRF innovation doctoral scholarship
- Connect Africa
- NRF
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research
Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, the understanding of the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4(+) T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4(+) T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1* 1101 was associated with HIV control (r = - 0.5, P = 0.02). These data identify an association between HIV-specific CD4(+) T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4(+) T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4(+) T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4(+) T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4(+) T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4(+) T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4(+) T cell responses targeting an immunodominant DRB1* 11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections.
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