PMID- 24906112
OWN - NLM
STAT- MEDLINE
DCOM- 20150601
LR  - 20211021
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 28
IP  - 14
DP  - 2014 Sep 10
TI  - Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope 
      specificity, T-cell receptor clonotype usage and antigen load.
PG  - 2007-21
AB  - 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.
FAU - Kloverpris, Henrik N
AU  - Kloverpris HN
FAU - McGregor, Reuben
AU  - McGregor R
FAU - McLaren, James E
AU  - McLaren JE
FAU - Ladell, Kristin
AU  - Ladell K
FAU - Stryhn, Anette
AU  - Stryhn A
FAU - Koofhethile, Catherine
AU  - Koofhethile C
FAU - Brener, Jacqui
AU  - Brener J
FAU - Chen, Fabian
AU  - Chen F
FAU - Riddell, Lynn
AU  - Riddell L
FAU - Graziano, Luzzi
AU  - Graziano L
FAU - Klenerman, Paul
AU  - Klenerman P
FAU - Leslie, Alasdair
AU  - Leslie A
FAU - Buus, Soren
AU  - Buus S
FAU - Price, David A
AU  - Price DA
FAU - Goulder, Philip
AU  - Goulder P
LA  - eng
GR  - 091663/Wellcome Trust/United Kingdom
GR  - 100326/Wellcome Trust/United Kingdom
GR  - R01 AI046995/AI/NIAID NIH HHS/United States
GR  - R01 AI46995/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Anti-HIV Agents/pharmacology
MH  - CD8-Positive T-Lymphocytes/drug effects/*immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HIV/*immunology
MH  - HIV Infections/drug therapy/genetics/*immunology
MH  - Humans
MH  - Immunodominant Epitopes/*immunology
MH  - Lymphocyte Activation
MH  - Programmed Cell Death 1 Receptor/*immunology
MH  - Receptors, Antigen, T-Cell/immunology
PMC - PMC4166042
EDAT- 2014/06/07 06:00
MHDA- 2015/06/02 06:00
PMCR- 2014/09/17
CRDT- 2014/06/07 06:00
PHST- 2014/06/07 06:00 [entrez]
PHST- 2014/06/07 06:00 [pubmed]
PHST- 2015/06/02 06:00 [medline]
PHST- 2014/09/17 00:00 [pmc-release]
AID - 10.1097/QAD.0000000000000362 [doi]
PST - ppublish
SO  - AIDS. 2014 Sep 10;28(14):2007-21. doi: 10.1097/QAD.0000000000000362.