High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted Gag-derived epitopes associated with relative HIV control.
Details
Serval ID
serval:BIB_B1B156BF9107
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted Gag-derived epitopes associated with relative HIV control.
Journal
Journal of virology
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
09/2011
Peer-reviewed
Oui
Volume
85
Number
18
Pages
9334-9345
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Virus-specific cytotoxic T lymphocytes (CTL) with high levels of functional avidity have been associated with viral clearance in hepatitis C virus infection and with enhanced antiviral protective immunity in animal models. However, the role of functional avidity as a determinant of HIV-specific CTL efficacy remains to be assessed. Here we measured the functional avidities of HIV-specific CTL responses targeting 20 different, optimally defined CTL epitopes restricted by 13 different HLA class I alleles in a cohort comprising 44 HIV controllers and 68 HIV noncontrollers. Responses restricted by HLA-B alleles and responses targeting epitopes located in HIV Gag exhibited significantly higher functional avidities than responses restricted by HLA-A or HLA-C molecules (P = 0.0003) or responses targeting epitopes outside Gag (P < 0.0001). The functional avidities of Gag-specific and HLA-B-restricted responses were higher in HIV controllers than in noncontrollers (P = 0.014 and P = 0.018) and were not restored in HIV noncontrollers initiating antiretroviral therapy. T-cell receptor (TCR) analyses revealed narrower TCR repertoires in higher-avidity CTL populations, which were dominated by public TCR sequences in HIV controllers. Together, these data link the presence of high-avidity Gag-specific and HLA-B-restricted CTL responses with viral suppression in vivo and provide new insights into the immune parameters that mediate spontaneous control of HIV infection.
Keywords
Cohort Studies, Epitopes/immunology, HIV Infections/immunology, HIV Long-Term Survivors, HLA-A Antigens/immunology, HLA-B Antigens/immunology, HLA-C Antigens/immunology, Humans, Receptors, Antigen, T-Cell/analysis, T-Lymphocytes, Cytotoxic/immunology, gag Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
09/05/2023 13:00
Last modification date
29/11/2024 13:31