Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality.

Virology
Nompumelelo P MkhwanaziThumbi Ndung'u

Abstract

HIV-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-gamma, TNF-alpha, IL-2, MIP-1beta, 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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Citations

Mar 1, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Marianne W MureithiUNKNOWN CAPRISA004 Trial Group
Dec 21, 2010·Immunologic Research·Stephanie A FreelGeorgia D Tomaras
Mar 2, 2011·Immunology·Marie-Eve BlaisSarah Rowland-Jones
Jul 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ushani S RajapaksaXiao-Ning Xu
Apr 5, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie-Eve BlaisSarah L Rowland-Jones

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Methods Mentioned

BETA
flow cytometry
PCR
FCS

Software Mentioned

DIVA
Roche Amplicor
FlowJo
PESTLE
TreeStar
ClustalX
SPICE
Sequencer
HLA
Bioedit

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