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Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells
Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC m...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244027/ https://www.ncbi.nlm.nih.gov/pubmed/22162830 http://dx.doi.org/10.1084/jem.20110640 |
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author | Ireland, Jamie M. Unanue, Emil R. |
author_facet | Ireland, Jamie M. Unanue, Emil R. |
author_sort | Ireland, Jamie M. |
collection | PubMed |
description | Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on B cells or B lymphoma cells under normal culture conditions. In B cells, engagement of the B cell antigen receptor was required for presentation of the citrullinated peptides, also inhibited by 3MA. B lymphoma–expressing HEL cells presented citrullinated peptides only after brief serum starvation. This presentation was reduced by 3MA or by reduction in Atg5 expression. Presentation of the unmodified peptides was not changed. The findings indicate a linkage between autophagy and autoreactivity through the generation of this neo-epitope. |
format | Online Article Text |
id | pubmed-3244027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32440272012-06-19 Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells Ireland, Jamie M. Unanue, Emil R. J Exp Med Brief Definitive Report Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on B cells or B lymphoma cells under normal culture conditions. In B cells, engagement of the B cell antigen receptor was required for presentation of the citrullinated peptides, also inhibited by 3MA. B lymphoma–expressing HEL cells presented citrullinated peptides only after brief serum starvation. This presentation was reduced by 3MA or by reduction in Atg5 expression. Presentation of the unmodified peptides was not changed. The findings indicate a linkage between autophagy and autoreactivity through the generation of this neo-epitope. The Rockefeller University Press 2011-12-19 /pmc/articles/PMC3244027/ /pubmed/22162830 http://dx.doi.org/10.1084/jem.20110640 Text en © 2011 Ireland and Unanue This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Ireland, Jamie M. Unanue, Emil R. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title | Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title_full | Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title_fullStr | Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title_full_unstemmed | Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title_short | Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells |
title_sort | autophagy in antigen-presenting cells results in presentation of citrullinated peptides to cd4 t cells |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244027/ https://www.ncbi.nlm.nih.gov/pubmed/22162830 http://dx.doi.org/10.1084/jem.20110640 |
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