Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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, Volume 28, No. 14, Year 2014
Notification
URL copied to clipboard!
Description
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 Wolters Kluwer Health.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4166042/bin/aids-28-2007-s001.pdf
Authors & Co-Authors
Kløverpris, Henrik N.
United Kingdom, Oxford
University of Oxford
Denmark, Copenhagen
Københavns Universitet
South Africa, Durban
The Nelson R. Mandela Medical School
McGregor, Reuben
United Kingdom, Oxford
University of Oxford
McLaren, James E.
United Kingdom, Cardiff
Cardiff University
Ladell, Kristin
United Kingdom, Cardiff
Cardiff University
Stryhn, Anette
Denmark, Copenhagen
Københavns Universitet
Koofhethile, Catherine Kegakilwe
United Kingdom, Oxford
University of Oxford
Brener, Jacqui
United Kingdom, Oxford
University of Oxford
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Riddell, Lynn A.
United Kingdom, Northampton
Northampton General Hospital
Graziano, Luzzi
United Kingdom, High Wycombe
Wycombe Hospital
Klenerman, Paul
United Kingdom, Oxford
Nuffield Department of Medicine
Leslie, Alasdair J.
South Africa, Durban
The Nelson R. Mandela Medical School
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Price, David Ashley
United Kingdom, Cardiff
Cardiff University
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 15
Authors: 15
Affiliations: 9
Identifiers
Doi:
10.1097/QAD.0000000000000362
e-ISSN:
14735571
Research Areas
Genetics And Genomics
Infectious Diseases