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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 Edward, Ladell, Kristin Ingrid, Stryhn, Anette, Koofhethile, Catherine, Brener, Jacqui, Chen, Fabian, Riddell, Lynn, Graziano, Luzzi, Klenerman, Paul, Leslie, Alasdair, Buus, Søren, Price, David and Goulder, Philip 2014. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load. AIDS 28 (14) , pp. 2007-2021. 10.1097/QAD.0000000000000362

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: Lippincott Williams & Wilkins
ISSN: 0269-9370
Funders: Wellcome
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 22 May 2014
Last Modified: 06 Feb 2019 16:54
URI: http://orca.cf.ac.uk/id/eprint/75921

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Cited 5 times in Web of Science. View in Web of Science.

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