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Mice completely lacking immunoproteasomes display major alterations in antigen presentation

The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes have not been previously developed. Here we show that dendritic cells from mice lacking the three immunoproteasome catalytic subunits display defects in presenting multiple...

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Autores principales: Kincaid, Eleanor Z, Che, Jenny W, York, Ian, Escobar, Hernando, Reyes-Vargas, Eduardo, Delgado, Julio C., Welsh, Raymond M, Karow, Margaret L., Murphy, Andrew J., Valenzuela, David M., Yancopoulos, George D., Rock, Kenneth L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262888/
https://www.ncbi.nlm.nih.gov/pubmed/22197977
http://dx.doi.org/10.1038/ni.2203
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author Kincaid, Eleanor Z
Che, Jenny W
York, Ian
Escobar, Hernando
Reyes-Vargas, Eduardo
Delgado, Julio C.
Welsh, Raymond M
Karow, Margaret L.
Murphy, Andrew J.
Valenzuela, David M.
Yancopoulos, George D.
Rock, Kenneth L
author_facet Kincaid, Eleanor Z
Che, Jenny W
York, Ian
Escobar, Hernando
Reyes-Vargas, Eduardo
Delgado, Julio C.
Welsh, Raymond M
Karow, Margaret L.
Murphy, Andrew J.
Valenzuela, David M.
Yancopoulos, George D.
Rock, Kenneth L
author_sort Kincaid, Eleanor Z
collection PubMed
description The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes have not been previously developed. Here we show that dendritic cells from mice lacking the three immunoproteasome catalytic subunits display defects in presenting multiple major histocompatability (MHC) class I epitopes. During viral infection in vivo, the presentation of a majority of MHC class I epitopes is markedly reduced in immunoproteasome-deficient animals, while presentation of MHC class II peptides is unaffected. By mass spectrometry the repertoire of MHC class I-presented peptides is ~50% different and these differences are sufficient to stimulate robust transplant rejection of wild type cells in mutant mice. These results indicate that immunoproteasomes play a much more important role in antigen presentation than previously thought.
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spelling pubmed-32628882012-08-01 Mice completely lacking immunoproteasomes display major alterations in antigen presentation Kincaid, Eleanor Z Che, Jenny W York, Ian Escobar, Hernando Reyes-Vargas, Eduardo Delgado, Julio C. Welsh, Raymond M Karow, Margaret L. Murphy, Andrew J. Valenzuela, David M. Yancopoulos, George D. Rock, Kenneth L Nat Immunol Article The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes have not been previously developed. Here we show that dendritic cells from mice lacking the three immunoproteasome catalytic subunits display defects in presenting multiple major histocompatability (MHC) class I epitopes. During viral infection in vivo, the presentation of a majority of MHC class I epitopes is markedly reduced in immunoproteasome-deficient animals, while presentation of MHC class II peptides is unaffected. By mass spectrometry the repertoire of MHC class I-presented peptides is ~50% different and these differences are sufficient to stimulate robust transplant rejection of wild type cells in mutant mice. These results indicate that immunoproteasomes play a much more important role in antigen presentation than previously thought. 2011-12-25 /pmc/articles/PMC3262888/ /pubmed/22197977 http://dx.doi.org/10.1038/ni.2203 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kincaid, Eleanor Z
Che, Jenny W
York, Ian
Escobar, Hernando
Reyes-Vargas, Eduardo
Delgado, Julio C.
Welsh, Raymond M
Karow, Margaret L.
Murphy, Andrew J.
Valenzuela, David M.
Yancopoulos, George D.
Rock, Kenneth L
Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title_full Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title_fullStr Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title_full_unstemmed Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title_short Mice completely lacking immunoproteasomes display major alterations in antigen presentation
title_sort mice completely lacking immunoproteasomes display major alterations in antigen presentation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262888/
https://www.ncbi.nlm.nih.gov/pubmed/22197977
http://dx.doi.org/10.1038/ni.2203
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