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PMID: 10716924 Published · ppublish English Journal Article

Functional HLA-DM on the surface of B cells and immature dendritic cells.

The EMBO journal ·Vol. 19 ·No. 6 ·2000-03-15 ·Pages 1241-51

Arndt SO, Vogt AB, Markovic-Plese S, Martin R, Moldenhauer G, Wölpl A, Sun Y, Schadendorf D, Hämmerling GJ, Kropshofer H

Abstract

HLA-DM (DM) plays a critical role in antigen presentation through major histocompatibility complex (MHC) class II molecules. DM functions as a molecular chaperone by keeping class II molecules competent for antigenic peptide loading and serves as an editor by favoring presentation of high-stability peptides. Until now, DM has been thought to exert these activities only in late endosomal/lysosomal compartments of antigen-presenting cells. Here we show that a subset of DM resides at the cell surface of B cells and immature dendritic cells. Surface DM engages in complexes with putatively empty class II molecules and controls presentation of those antigens that rely on loading on the cell surface or in early endosomal recycling compartments. For example, epitopes derived from myelin basic protein that are implicated in the autoimmune disease multiple sclerosis are down-modulated by DM, but are presented in the absence of DM. Thus, this novel concept of functional DM on the surface may be relevant to both protective immune responses and autoimmunity.

MeSH Terms
Amino Acid Sequence Antigen Presentation/immunology Autoantigens/immunology,metabolism B-Lymphocytes/cytology,immunology,metabolism Cell Differentiation Cell Membrane/chemistry,metabolism Cells, Cultured Dendritic Cells/cytology,immunology,metabolism Down-Regulation Endocytosis Endosomes/chemistry,metabolism Epitopes, B-Lymphocyte/immunology,metabolism HLA-D Antigens/immunology,metabolism HLA-DR Antigens/immunology,metabolism Histocompatibility Antigens Class II/immunology,metabolism Humans Lymphocyte Activation/immunology Membrane Proteins/immunology,metabolism Molecular Sequence Data Myelin Basic Protein/immunology,metabolism Peptide Fragments/immunology,metabolism Protein Binding T-Lymphocytes/cytology,immunology
Chemicals
Autoantigens Epitopes, B-Lymphocyte H2-M antigens HLA-D Antigens HLA-DM antigens HLA-DR Antigens Histocompatibility Antigens Class II Membrane Proteins Myelin Basic Protein Peptide Fragments
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Arndt S O
Department of Molecular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
Vogt A B
Markovic-Plese S
Martin R
Moldenhauer G
Wölpl A
Sun Y
Schadendorf D
Hämmerling G J
Kropshofer H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.6.1241
Published
2000-03-15
Pages
1241-51
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305665
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.6.1241 PMC Full Text View journal details
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