Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

Major histocompatibility class II (MHCII) molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs). This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (D...

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Main Author: Lisa K. Denzin
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00465/full
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author Lisa K. Denzin
author_facet Lisa K. Denzin
author_sort Lisa K. Denzin
collection DOAJ
description Major histocompatibility class II (MHCII) molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs). This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM). DM activity is directly opposed by HLA-DO (DO), another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.
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spelling doaj.art-0b7d52a81a4b412cac34daefc87499122022-12-22T00:18:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-12-01410.3389/fimmu.2013.0046565897Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self toleranceLisa K. Denzin0Rutgers Robert Wood Johnson Medical SchooolMajor histocompatibility class II (MHCII) molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs). This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM). DM activity is directly opposed by HLA-DO (DO), another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00465/fullAntigen PresentationAutoimmunitydiabetesgerminal center reactionMHC class IIHLA-DM
spellingShingle Lisa K. Denzin
Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
Frontiers in Immunology
Antigen Presentation
Autoimmunity
diabetes
germinal center reaction
MHC class II
HLA-DM
title Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
title_full Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
title_fullStr Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
title_full_unstemmed Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
title_short Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance
title_sort inhibition of hla dm mediated mhc class ii peptide loading by hla do promotes self tolerance
topic Antigen Presentation
Autoimmunity
diabetes
germinal center reaction
MHC class II
HLA-DM
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00465/full
work_keys_str_mv AT lisakdenzin inhibitionofhladmmediatedmhcclassiipeptideloadingbyhladopromotesselftolerance