Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality
Thobakgale, Christina F.
van der Stok, Mary
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CitationMkhwanazi, Nompumelelo, Christina F. Thobakgale, Mary van der Stok, Shabashini Reddy, Zenele Mncube, Fundisiwe Chonco, Bruce D. Walker, Marcus Altfeld, Philip J. R. Goulder, and Thumbi Ndung'u. 2010. Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality. Virology 405(2-3): 483-491.
AbstractHIV-1 specific HLA-B-restricted CD8+ T cell responses differ from HLA-C-restricted responses in antiviral effectiveness. To investigate possible reasons for these differences, we characterized the frequency and polyfunctionality of immmunodominant HLA-B*57/B5801- and HLA-Cw*07-restricted CD8+ T cells occurring concurrently in nine study subjects assessing IFN-γ, TNF-α, IL-2, MIP-1β, and CD107a by flow cytometry and analyzed sequence variation in targeted epitopes. HLA-B*57/5801 and HLA-Cw*07 restricted CD8+ T cells did not differ significantly in polyfunctionality (p = 0.84). Possession of three or more functions correlated positively with CD4+ T cell counts (r = 0.85; p = 0.006) and monofunctional CD8+ T cells inversely correlated with CD4 cell counts (r = −0.79; p = 0.05). There were no differences in polyfunctionality of CD8+ T cells specific to wildtype versus mutated epitopes. These results suggest that loss of polyfunctionality and increase in monofunctional HIV-1-specific CD8+ T cells are associated with disease progression independent of restricting HLA allele. Furthermore, sequence variation does not appear to significantly impact CD8+ T cell polyfunctionality in chronic HIV-1 infection.
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