No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repea...

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Autores principales:	Slobodan Culina, François-Xavier Mauvais, Hsiang-Ting Hsu, Anne Burgevin, Suzanne Guénette, Anna Moser, Peter van Endert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c17794ffb1494ec3a8a902f1e3c68dc4
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spelling	oai:doaj.org-article:c17794ffb1494ec3a8a902f1e3c68dc42021-11-18T08:33:16ZNo major role for insulin-degrading enzyme in antigen presentation by MHC molecules.1932-620310.1371/journal.pone.0088365https://doaj.org/article/c17794ffb1494ec3a8a902f1e3c68dc42014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24516642/?tool=EBIhttps://doaj.org/toc/1932-6203Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE) was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.Slobodan CulinaFrançois-Xavier MauvaisHsiang-Ting HsuAnne BurgevinSuzanne GuénetteAnna MoserPeter van EndertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88365 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Slobodan Culina François-Xavier Mauvais Hsiang-Ting Hsu Anne Burgevin Suzanne Guénette Anna Moser Peter van Endert No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
description	Antigen presentation by MHC class I molecules requires degradation of epitope source proteins in the cytosol. Although the preeminent role of the proteasome is clearly established, evidence suggesting a significant role for proteasome-independent generation of class I ligands has been reported repeatedly. However, an enzyme responsible for such a role has not been identified. Recently insulin-degrading enzyme (IDE) was shown to produce an antigenic peptide derived from the tumor antigen MAGE-A3 in an entirely proteasome-independent manner, raising the question of the global impact of IDE in MHC class I antigen processing. Here we report that IDE knockdown in human cell lines, or knockout in two different mouse strains, has no effect on cell surface expression of various MHC class I molecules, including allomorphs such as HLA-A3 and HLA-B27 suggested to be loaded in an at least a partly proteasome-independent manner. Moreover, reduced or absent IDE expression does not affect presentation of five epitopes including epitopes derived from beta amyloid and proinsulin, two preferred IDE substrates. Thus, IDE does not play a major role in MHC class I antigen processing, confirming the dominant and almost exclusive role of the proteasome in cytosolic production of MHC class I ligands.
format	article
author	Slobodan Culina François-Xavier Mauvais Hsiang-Ting Hsu Anne Burgevin Suzanne Guénette Anna Moser Peter van Endert
author_facet	Slobodan Culina François-Xavier Mauvais Hsiang-Ting Hsu Anne Burgevin Suzanne Guénette Anna Moser Peter van Endert
author_sort	Slobodan Culina
title	No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
title_short	No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
title_full	No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
title_fullStr	No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
title_full_unstemmed	No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.
title_sort	no major role for insulin-degrading enzyme in antigen presentation by mhc molecules.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c17794ffb1494ec3a8a902f1e3c68dc4
work_keys_str_mv	AT slobodanculina nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT francoisxaviermauvais nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT hsiangtinghsu nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT anneburgevin nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT suzanneguenette nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT annamoser nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules AT petervanendert nomajorroleforinsulindegradingenzymeinantigenpresentationbymhcmolecules
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No major role for insulin-degrading enzyme in antigen presentation by MHC molecules.

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