Cargando…

Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein

BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This sp...

Descripción completa

Detalles Bibliográficos
Autores principales: Lorente, Elena, Barriga, Alejandro, García-Arriaza, Juan, Lemonnier, François A., Esteban, Mariano, López, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679651/
https://www.ncbi.nlm.nih.gov/pubmed/29084215
http://dx.doi.org/10.1371/journal.pntd.0006036
_version_ 1783277622566846464
author Lorente, Elena
Barriga, Alejandro
García-Arriaza, Juan
Lemonnier, François A.
Esteban, Mariano
López, Daniel
author_facet Lorente, Elena
Barriga, Alejandro
García-Arriaza, Juan
Lemonnier, François A.
Esteban, Mariano
López, Daniel
author_sort Lorente, Elena
collection PubMed
description BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized. METHODOLOGY/PRINCIPAL FINDINGS: By infection of HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes are presented by the common HLA class I molecule, HLA-A*0201. One of these epitopes is processed and presented via a complex pathway that involves proteases from different subcellular locations. Specific chemical inhibitors blocked these events in rVACV-CHIKV-infected cells. CONCLUSIONS/SIGNIFICANCE: Our data have implications not only for the identification of novel Alphavirus and Togaviridae antiviral CTL responses, but also for analyzing presentation of antigen from viruses of different families and orders that use host proteinases to generate their mature envelope proteins.
format Online
Article
Text
id pubmed-5679651
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-56796512017-11-18 Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein Lorente, Elena Barriga, Alejandro García-Arriaza, Juan Lemonnier, François A. Esteban, Mariano López, Daniel PLoS Negl Trop Dis Research Article BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized. METHODOLOGY/PRINCIPAL FINDINGS: By infection of HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes are presented by the common HLA class I molecule, HLA-A*0201. One of these epitopes is processed and presented via a complex pathway that involves proteases from different subcellular locations. Specific chemical inhibitors blocked these events in rVACV-CHIKV-infected cells. CONCLUSIONS/SIGNIFICANCE: Our data have implications not only for the identification of novel Alphavirus and Togaviridae antiviral CTL responses, but also for analyzing presentation of antigen from viruses of different families and orders that use host proteinases to generate their mature envelope proteins. Public Library of Science 2017-10-30 /pmc/articles/PMC5679651/ /pubmed/29084215 http://dx.doi.org/10.1371/journal.pntd.0006036 Text en © 2017 Lorente et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lorente, Elena
Barriga, Alejandro
García-Arriaza, Juan
Lemonnier, François A.
Esteban, Mariano
López, Daniel
Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title_full Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title_fullStr Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title_full_unstemmed Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title_short Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein
title_sort complex antigen presentation pathway for an hla-a*0201-restricted epitope from chikungunya 6k protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679651/
https://www.ncbi.nlm.nih.gov/pubmed/29084215
http://dx.doi.org/10.1371/journal.pntd.0006036
work_keys_str_mv AT lorenteelena complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein
AT barrigaalejandro complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein
AT garciaarriazajuan complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein
AT lemonnierfrancoisa complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein
AT estebanmariano complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein
AT lopezdaniel complexantigenpresentationpathwayforanhlaa0201restrictedepitopefromchikungunya6kprotein