AIDS

Skip Navigation LinksHome > September 10, 2014 - Volume 28 - Issue 14 > Programmed death-1 expression on HIV-1-specific CD8+ T cells...
AIDS:
doi: 10.1097/QAD.0000000000000362
Basic Science

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.a,c,h; McGregor, Reubena; McLaren, James E.b; Ladell, Kristinb; Stryhn, Anettec; Koofhethile, Catherinea; Brener, Jacquia; Chen, Fabiand; Riddell, Lynne; Graziano, Luzzif; Klenerman, Paulg; Leslie, Alasdairh; Buus, Sørenc; Price, David A.b,i,*; Goulder, Philipa,*

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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 (PD-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 PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-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 PD-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 PD-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 PD-1 expression levels are influenced by peptide/HLA class I antigen exposure.

© 2014 Lippincott Williams & Wilkins, Inc.

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