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 ORCID: https://orcid.org/0000-0002-7021-5934, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Stryhn, Anette, Koofhethile, Catherine, Brener, Jacqui, Chen, Fabian, Riddell, Lynn, Graziano, Luzzi, Klenerman, Paul, Leslie, Alasdair, Buus, Søren, Price, David ORCID: https://orcid.org/0000-0001-9416-2737 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:	05 May 2023 17:05
URI:	https://orca.cardiff.ac.uk/id/eprint/75921

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