Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller

The analysis of T-cell responses in HIV-1-infected controllers may contribute to a better understanding of the protective components of the immune system. Here, we analyzed the HIV-1-specific T-cell response in a 59-year-old HIV-1-infected controller, infected for at least seven years, who presented...

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Main Authors: Boutaina El Kenz, Katja G. Schmidt, Victoria K. Ogungbemi-Alt, Silke Bergmann, Philipp Steininger, Klaus Korn, Bernd Spriewald, Ellen G. Harrer, Krystelle Nganou-Makamdop, Thomas Harrer
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/2/567
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author Boutaina El Kenz
Katja G. Schmidt
Victoria K. Ogungbemi-Alt
Silke Bergmann
Philipp Steininger
Klaus Korn
Bernd Spriewald
Ellen G. Harrer
Krystelle Nganou-Makamdop
Thomas Harrer
author_facet Boutaina El Kenz
Katja G. Schmidt
Victoria K. Ogungbemi-Alt
Silke Bergmann
Philipp Steininger
Klaus Korn
Bernd Spriewald
Ellen G. Harrer
Krystelle Nganou-Makamdop
Thomas Harrer
author_sort Boutaina El Kenz
collection DOAJ
description The analysis of T-cell responses in HIV-1-infected controllers may contribute to a better understanding of the protective components of the immune system. Here, we analyzed the HIV-1-specific T-cell response in a 59-year-old HIV-1-infected controller, infected for at least seven years, who presented with low viral loads ranging from <20 copies/mL to 200 copies/mL and normal CD4 counts of >800 cells/µL. In γ-IFN-ELISpot assays using freshly isolated PBMCs, he displayed a very strong polyclonal T-cell response to eight epitopes in Gag, Nef and Rev; with the dominant responses directed against the HLA-B*57-epitope AISPRTLNAW and against a so-far-unknown epitope within Rev. Further analyses using peptide-stimulated T-cell lines in γ-IFN-ELISpot assays delineated the peptide RQRQIRSI (Rev-RI8) as a newly defined HLA-B*52-restricted epitope located within a functionally important region of Rev. Peptide-stimulation assays in 15 HLA-B*52-positive HIV-1-infected subjects, including the controller, demonstrated recognition of the Rev-RI8 epitope in 6/15 subjects. CD4 counts before the start of antiviral therapy were significantly higher in subjects with recognition of the Rev-RI8 epitope. Targeting of the Rev-RI8 epitope in Rev by CTL could contribute to the positive association of HLA-B*52 with a more favorable course of HIV-1-infection.
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spelling doaj.art-1cf176c9fc654103bbae9ff2076fcdc12023-11-16T23:50:46ZengMDPI AGViruses1999-49152023-02-0115256710.3390/v15020567Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected ControllerBoutaina El Kenz0Katja G. Schmidt1Victoria K. Ogungbemi-Alt2Silke Bergmann3Philipp Steininger4Klaus Korn5Bernd Spriewald6Ellen G. Harrer7Krystelle Nganou-Makamdop8Thomas Harrer9Infectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInfectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInfectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInfectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Internal Medicine 5, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInfectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyInfectious Diseases and Immunodeficiency Section, Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyThe analysis of T-cell responses in HIV-1-infected controllers may contribute to a better understanding of the protective components of the immune system. Here, we analyzed the HIV-1-specific T-cell response in a 59-year-old HIV-1-infected controller, infected for at least seven years, who presented with low viral loads ranging from <20 copies/mL to 200 copies/mL and normal CD4 counts of >800 cells/µL. In γ-IFN-ELISpot assays using freshly isolated PBMCs, he displayed a very strong polyclonal T-cell response to eight epitopes in Gag, Nef and Rev; with the dominant responses directed against the HLA-B*57-epitope AISPRTLNAW and against a so-far-unknown epitope within Rev. Further analyses using peptide-stimulated T-cell lines in γ-IFN-ELISpot assays delineated the peptide RQRQIRSI (Rev-RI8) as a newly defined HLA-B*52-restricted epitope located within a functionally important region of Rev. Peptide-stimulation assays in 15 HLA-B*52-positive HIV-1-infected subjects, including the controller, demonstrated recognition of the Rev-RI8 epitope in 6/15 subjects. CD4 counts before the start of antiviral therapy were significantly higher in subjects with recognition of the Rev-RI8 epitope. Targeting of the Rev-RI8 epitope in Rev by CTL could contribute to the positive association of HLA-B*52 with a more favorable course of HIV-1-infection.https://www.mdpi.com/1999-4915/15/2/567HIV-1 infectionelite controllerCTLepitopeRevHLA B*52
spellingShingle Boutaina El Kenz
Katja G. Schmidt
Victoria K. Ogungbemi-Alt
Silke Bergmann
Philipp Steininger
Klaus Korn
Bernd Spriewald
Ellen G. Harrer
Krystelle Nganou-Makamdop
Thomas Harrer
Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
Viruses
HIV-1 infection
elite controller
CTL
epitope
Rev
HLA B*52
title Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
title_full Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
title_fullStr Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
title_full_unstemmed Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
title_short Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller
title_sort definition of a new hla b 52 restricted rev ctl epitope targeted by an hiv 1 infected controller
topic HIV-1 infection
elite controller
CTL
epitope
Rev
HLA B*52
url https://www.mdpi.com/1999-4915/15/2/567
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