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AIDS:
doi: 10.1097/QAD.0000000000000362
Original paper: PDF Only

Programmed death-1 expression on HIV-1 specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load.

Kløverpris, Henrik N.; McGregor, Reuben; Mclaren, James E.; Ladell, Kristin; Stryhn, Anette; Koofhethile, Catherine; Brener, Jacqui; Chen, Fabian; Riddell, Lynn; Graziano, Luzzi; Klenerman, Paul; Leslie, Alasdair; Buus, Søren; Price, David A.; Goulder, Philip

Supplemental Author Material
Published Ahead-of-Print
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Abstract

Objectives: Although CD8+ T cells play a critical role in the control of HIV-1 infection, their antiviral efficacy can be limited by antigenic variation and immune exhaustion. The latter phenomenon is characterized by the upregulation of multiple inhibitory receptors, such as programmed death-1, CD244 and lymphocyte activation gene-3 (LAG-3), which modulate the functional capabilities of CD8+ T cells.

Design and methods: Here, we used an array of different human leukocyte antigen (HLA)-B*15 : 03 and HLA-B*42 : 01 tetramers to characterize inhibitory receptor expression as a function of differentiation on HIV-1-specific CD8+ T-cell populations (n = 128) spanning 11 different epitope targets.

Results: Expression levels of programmed death-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of programmed death-1 on T-cell receptor (TCR) clonotypes within individual HIV-1-specific CD8+ T-cell populations was also apparent, independent of clonal dominance hierarchies. Positive correlations were detected between programmed death-1 expression and plasma viral load, which were reinforced by stratification for epitope sequence stability and dictated by effector memory CD8+ T cells.

Conclusion: Collectively, these data suggest that programmed death-1 expression on HIV-1-specific CD8+ T cells tracks antigen load at the level of epitope specificity and TCR clonotype usage. These findings are important because they provide evidence that programmed death-1 expression levels are influenced by peptide/HLA class I antigen exposure.

(C) 2014 Lippincott Williams & Wilkins, Inc.

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