Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.

HLA-B*27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B*27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B...

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Autores principales:	Julia Schmidt, Astrid K N Iversen, Stefan Tenzer, Emma Gostick, David A Price, Volker Lohmann, Ute Distler, Paul Bowness, Hansjörg Schild, Hubert E Blum, Paul Klenerman, Christoph Neumann-Haefelin, Robert Thimme
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c948d12be085467aa0d4b5ccb27562d4
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spelling	oai:doaj.org-article:c948d12be085467aa0d4b5ccb27562d42021-11-18T06:06:19ZRapid antigen processing and presentation of a protective and immunodominant HLA-B27-restricted hepatitis C virus-specific CD8+ T-cell epitope.1553-73661553-737410.1371/journal.ppat.1003042https://doaj.org/article/c948d12be085467aa0d4b5ccb27562d42012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23209413/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HLA-B27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B27-restricted CD8+ T-cell epitopes contributes to this phenomenon in both infections. Indeed, protection can be linked to single immunodominant CD8+ T-cell epitopes and functional constraints on escape mutations within these epitopes. To better define the immunological mechanisms underlying HLA-B27-mediated protection in HCV infection, we analyzed the functional avidity, functional profile, antiviral efficacy and naïve precursor frequency of CD8+ T cells targeting the immunodominant HLA-B27-restricted HCV-specific epitope as well as its antigen processing and presentation. For comparison, HLA-A02-restricted HCV-specific epitopes were analyzed. The HLA-B27-restricted CD8+ T-cell epitope was not superior to epitopes restricted by HLA-A02 when considering the functional avidity, functional profile, antiviral efficacy or naïve precursor frequency. However, the peptide region containing the HLA-B27-restricted epitope was degraded extremely fast by both the constitutive proteasome and the immunoproteasome. This efficient proteasomal processing that could be blocked by proteasome inhibitors was highly dependent on the hydrophobic regions flanking the epitope and led to rapid and abundant presentation of the epitope on the cell surface of antigen presenting cells. Our data suggest that rapid antigen processing may be a key immunological feature of this protective and immunodominant HLA-B*27-restricted HCV-specific epitope.Julia SchmidtAstrid K N IversenStefan TenzerEmma GostickDavid A PriceVolker LohmannUte DistlerPaul BownessHansjörg SchildHubert E BlumPaul KlenermanChristoph Neumann-HaefelinRobert ThimmePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 11, p e1003042 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Julia Schmidt Astrid K N Iversen Stefan Tenzer Emma Gostick David A Price Volker Lohmann Ute Distler Paul Bowness Hansjörg Schild Hubert E Blum Paul Klenerman Christoph Neumann-Haefelin Robert Thimme Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
description	HLA-B27 exerts protective effects in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. While the immunological and virological features of HLA-B27-mediated protection are not fully understood, there is growing evidence that the presentation of specific immunodominant HLA-B27-restricted CD8+ T-cell epitopes contributes to this phenomenon in both infections. Indeed, protection can be linked to single immunodominant CD8+ T-cell epitopes and functional constraints on escape mutations within these epitopes. To better define the immunological mechanisms underlying HLA-B27-mediated protection in HCV infection, we analyzed the functional avidity, functional profile, antiviral efficacy and naïve precursor frequency of CD8+ T cells targeting the immunodominant HLA-B27-restricted HCV-specific epitope as well as its antigen processing and presentation. For comparison, HLA-A02-restricted HCV-specific epitopes were analyzed. The HLA-B27-restricted CD8+ T-cell epitope was not superior to epitopes restricted by HLA-A02 when considering the functional avidity, functional profile, antiviral efficacy or naïve precursor frequency. However, the peptide region containing the HLA-B27-restricted epitope was degraded extremely fast by both the constitutive proteasome and the immunoproteasome. This efficient proteasomal processing that could be blocked by proteasome inhibitors was highly dependent on the hydrophobic regions flanking the epitope and led to rapid and abundant presentation of the epitope on the cell surface of antigen presenting cells. Our data suggest that rapid antigen processing may be a key immunological feature of this protective and immunodominant HLA-B27-restricted HCV-specific epitope.
format	article
author	Julia Schmidt Astrid K N Iversen Stefan Tenzer Emma Gostick David A Price Volker Lohmann Ute Distler Paul Bowness Hansjörg Schild Hubert E Blum Paul Klenerman Christoph Neumann-Haefelin Robert Thimme
author_facet	Julia Schmidt Astrid K N Iversen Stefan Tenzer Emma Gostick David A Price Volker Lohmann Ute Distler Paul Bowness Hansjörg Schild Hubert E Blum Paul Klenerman Christoph Neumann-Haefelin Robert Thimme
author_sort	Julia Schmidt
title	Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
title_short	Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
title_full	Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
title_fullStr	Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
title_full_unstemmed	Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.
title_sort	rapid antigen processing and presentation of a protective and immunodominant hla-b*27-restricted hepatitis c virus-specific cd8+ t-cell epitope.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c948d12be085467aa0d4b5ccb27562d4
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Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope.

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