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Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages

The major histocompatibility complex (MHC) class II–associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a ∼3-kD peptide termed CLIP (class II–associated invariant...

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Autores principales: Shi, Guo-Ping, Bryant, Rebecca A.R., Riese, Richard, Verhelst, Steven, Driessen, Christoph, Li, Zhenqiang, Bromme, Dieter, Ploegh, Hidde L., Chapman, Harold A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193169/
https://www.ncbi.nlm.nih.gov/pubmed/10748235
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author Shi, Guo-Ping
Bryant, Rebecca A.R.
Riese, Richard
Verhelst, Steven
Driessen, Christoph
Li, Zhenqiang
Bromme, Dieter
Ploegh, Hidde L.
Chapman, Harold A.
author_facet Shi, Guo-Ping
Bryant, Rebecca A.R.
Riese, Richard
Verhelst, Steven
Driessen, Christoph
Li, Zhenqiang
Bromme, Dieter
Ploegh, Hidde L.
Chapman, Harold A.
author_sort Shi, Guo-Ping
collection PubMed
description The major histocompatibility complex (MHC) class II–associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a ∼3-kD peptide termed CLIP (class II–associated invariant chain peptide). Cathepsins L and S have both been implicated in degradation of Ii to CLIP in thymus and peripheral lymphoid organs, respectively. However, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto MHC class II dimers normally. Both processes are blocked by a cysteine protease inhibitor, indicating the involvement of an additional Ii-processing enzyme(s). Comparison of cysteine proteases expressed by macrophages with those found in splenocytes and dendritic cells revealed two enzymes expressed exclusively in macrophages, cathepsins Z and F. Recombinant cathepsin Z did not generate CLIP from Ii–MHC class II complexes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation. Inhibition of cathepsin F activity and MHC class II peptide loading by macrophages exhibited similar specificity and activity profiles. These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading.
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spelling pubmed-21931692008-04-16 Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages Shi, Guo-Ping Bryant, Rebecca A.R. Riese, Richard Verhelst, Steven Driessen, Christoph Li, Zhenqiang Bromme, Dieter Ploegh, Hidde L. Chapman, Harold A. J Exp Med Original Article The major histocompatibility complex (MHC) class II–associated invariant chain (Ii) regulates intracellular trafficking and peptide loading of MHC class II molecules. Such loading occurs after endosomal degradation of the invariant chain to a ∼3-kD peptide termed CLIP (class II–associated invariant chain peptide). Cathepsins L and S have both been implicated in degradation of Ii to CLIP in thymus and peripheral lymphoid organs, respectively. However, macrophages from mice deficient in both cathepsins S and L can process Ii and load peptides onto MHC class II dimers normally. Both processes are blocked by a cysteine protease inhibitor, indicating the involvement of an additional Ii-processing enzyme(s). Comparison of cysteine proteases expressed by macrophages with those found in splenocytes and dendritic cells revealed two enzymes expressed exclusively in macrophages, cathepsins Z and F. Recombinant cathepsin Z did not generate CLIP from Ii–MHC class II complexes, whereas cathepsin F was as efficient as cathepsin S in CLIP generation. Inhibition of cathepsin F activity and MHC class II peptide loading by macrophages exhibited similar specificity and activity profiles. These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading. The Rockefeller University Press 2000-04-03 /pmc/articles/PMC2193169/ /pubmed/10748235 Text en © 2000 The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Shi, Guo-Ping
Bryant, Rebecca A.R.
Riese, Richard
Verhelst, Steven
Driessen, Christoph
Li, Zhenqiang
Bromme, Dieter
Ploegh, Hidde L.
Chapman, Harold A.
Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title_full Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title_fullStr Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title_full_unstemmed Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title_short Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages
title_sort role for cathepsin f in invariant chain processing and major histocompatibility complex class ii peptide loading by macrophages
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193169/
https://www.ncbi.nlm.nih.gov/pubmed/10748235
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