In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 182.31-182.31
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 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 after infection), we determined all primary HIV-1 specific CD8+ T cell responses in 10 individuals from the RV217 early acute HIV-1 cohort. Participants are high-risk volunteers from Kenya and Thailand, and acute HIV-1 infection was determined from twice-weekly blood draws using a nucleic acid test. T cell responses were mapped against the unique infecting HIV-1 virus/es in each individual using IFN-γ ELISpot. Across participants, the immunodominant T cell response mostly targeted the Env, Gag and Pol proteins of the HIV-1 genome. We detected a wide (4–14 epitopes) breadth of T cell response across our cohort, with all HIV-1 proteins targeted and different rates of virus escape observed. The summed magnitude of response ranged from 1,388–16,044 SFU/106 cells. 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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.182.31
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2018
detail.hit.zdb_id:
1475085-5
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