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Joanna A Warren, Yinyan Xu, Margaret Costanzo, Victoria Whale, Michael P K Liu, Rasmi Thomas, Sodsai Tovanabutra, Gustavo Kijak, Leigh Anne Eller, Morgane Rolland, Nelson L Michael, Merlin L Robb, Michael A Eller, Nilu Goonetilleke, Understanding the determinants of CD8+ T cell immunodominance in acute HIV infection, The Journal of Immunology, Volume 198, Issue Supplement_1, May 2017, Page 151.14, https://doi.org/10.4049/jimmunol.198.Supp.151.14
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Abstract
CD8+ T cells detect and clear virus-infected cells. During human immunodeficiency virus-1 (HIV-1) infection, different HIV-specific CD8+ T cell populations are expanded, each targeting a discreet epitope. These different HIV-specific CD8+ T cell populations do not arise equally, and instead establish a hierarchy (immunodominance) based on strength of T cell response to a given viral epitope. Our previous work has shown that relative immunodominance is a major determinant of the rate at which HIV can mutate to escape T cell immune pressure. The precise mechanism of how the first CD8+ T cell response to HIV is generated, and which factors determine T cell dominance is unclear. To investigate determinants of T cell immunodominance in acute HIV-1 infection (~45 days following infection), we determined all primary HIV-1 specific CD8+ T cell responses in 10 individuals in the RV217 early HIV cohort (ECHO). T cell responses were mapped against the unique infecting HIV virus/es in each individual using IFN-γ ELISpot. Across participants, the dominant T cell response mostly targeted variable regions of the HIV-1 genome. We detected a wide (4–13 epitopes) breadth of T cell response across our cohort that was independent of HLA haplotype, with all HIV-1 proteins targeted and different rates of virus escape observed. Ongoing studies are focusing on better understanding how factors, such as T cell receptor repertoire, avidity, antigen presentation and function contribute to T cell immunodominance, which in turn will inform HIV-1 vaccine design.
