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TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I

Processing and presentation of antigen on MHC-I class I molecules serves to present peptides derived from cytosolic proteins to CD8(+) T cells. Infection with bacteria that remain in phagosomal compartments, such as Mycobacterium tuberculosis (Mtb), provides a challenge to this immune recognition as...

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Autores principales: Harriff, Melanie J., Burgdorf, Sven, Kurts, Christian, Wiertz, Emmanuel J. H. J., Lewinsohn, Deborah A., Lewinsohn, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823705/
https://www.ncbi.nlm.nih.gov/pubmed/24244525
http://dx.doi.org/10.1371/journal.pone.0079571
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author Harriff, Melanie J.
Burgdorf, Sven
Kurts, Christian
Wiertz, Emmanuel J. H. J.
Lewinsohn, Deborah A.
Lewinsohn, David M.
author_facet Harriff, Melanie J.
Burgdorf, Sven
Kurts, Christian
Wiertz, Emmanuel J. H. J.
Lewinsohn, Deborah A.
Lewinsohn, David M.
author_sort Harriff, Melanie J.
collection PubMed
description Processing and presentation of antigen on MHC-I class I molecules serves to present peptides derived from cytosolic proteins to CD8(+) T cells. Infection with bacteria that remain in phagosomal compartments, such as Mycobacterium tuberculosis (Mtb), provides a challenge to this immune recognition as bacterial proteins are segregated from the cytosol. Previously we identified the Mtb phagosome itself as an organelle capable of loading MHC Class I molecules with Mtb antigens. Here, we find that the TAP transporter, responsible for importing peptides into the ER for loading in Class I molecules, is both present and functional in Mtb phagosomes. Furthermore, we describe a novel peptide reagent, representing the N-terminal domain of the bovine herpes virus UL49.5 protein, which is capable of specifically inhibiting the lumenal face of TAP. Together, these results provide insight into the mechanism by which peptides from intra-phagosomal pathogens are loaded onto Class I molecules.
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spelling pubmed-38237052013-11-15 TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I Harriff, Melanie J. Burgdorf, Sven Kurts, Christian Wiertz, Emmanuel J. H. J. Lewinsohn, Deborah A. Lewinsohn, David M. PLoS One Research Article Processing and presentation of antigen on MHC-I class I molecules serves to present peptides derived from cytosolic proteins to CD8(+) T cells. Infection with bacteria that remain in phagosomal compartments, such as Mycobacterium tuberculosis (Mtb), provides a challenge to this immune recognition as bacterial proteins are segregated from the cytosol. Previously we identified the Mtb phagosome itself as an organelle capable of loading MHC Class I molecules with Mtb antigens. Here, we find that the TAP transporter, responsible for importing peptides into the ER for loading in Class I molecules, is both present and functional in Mtb phagosomes. Furthermore, we describe a novel peptide reagent, representing the N-terminal domain of the bovine herpes virus UL49.5 protein, which is capable of specifically inhibiting the lumenal face of TAP. Together, these results provide insight into the mechanism by which peptides from intra-phagosomal pathogens are loaded onto Class I molecules. Public Library of Science 2013-11-11 /pmc/articles/PMC3823705/ /pubmed/24244525 http://dx.doi.org/10.1371/journal.pone.0079571 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Harriff, Melanie J.
Burgdorf, Sven
Kurts, Christian
Wiertz, Emmanuel J. H. J.
Lewinsohn, Deborah A.
Lewinsohn, David M.
TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title_full TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title_fullStr TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title_full_unstemmed TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title_short TAP Mediates Import of Mycobacterium tuberculosis-Derived Peptides into Phagosomes and Facilitates Loading onto HLA-I
title_sort tap mediates import of mycobacterium tuberculosis-derived peptides into phagosomes and facilitates loading onto hla-i
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823705/
https://www.ncbi.nlm.nih.gov/pubmed/24244525
http://dx.doi.org/10.1371/journal.pone.0079571
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