Abstract
Complexes of peptide and major histocompatibility complex (MHC) class II are expressed on the surface of antigen-presenting cells but their molecular organization is unknown. Here we show that subsets of MHC class II molecules localize to membrane microdomains together with tetraspan proteins, the peptide editor HLA-DM and the costimulator CD86. Tetraspan microdomains differ from other membrane areas such as lipid rafts, as they enrich MHC class II molecules carrying a selected set of peptide antigens. Antigen-presenting cells deficient in tetraspan microdomains have a reduced capacity to activate CD4+ T cells. Thus, the organization of uniformly loaded peptide-MHC class II complexes in tetraspan domains may be a very early event that determines both the composition of the immunological synapse and the quality of the subsequent T helper cell response.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antibodies, Monoclonal / immunology
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Antigen Presentation*
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Antigens / immunology*
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Antigens, CD / immunology*
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Antigens, Differentiation, B-Lymphocyte / immunology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B7-2 Antigen
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CD4-Positive T-Lymphocytes / immunology*
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Cell Communication
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Cell Compartmentation
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Cell Line, Transformed
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Cyclodextrins / pharmacology
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Endosomes / metabolism
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HLA-D Antigens / immunology*
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HLA-DP Antigens / immunology
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HLA-DR Antigens / immunology
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Histocompatibility Antigens Class II / immunology*
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Humans
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Hybridomas / immunology
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation*
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Lysosomes / metabolism
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Macromolecular Substances
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Membrane Glycoproteins / immunology*
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Membrane Microdomains / drug effects
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Membrane Microdomains / immunology*
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Membrane Proteins / analysis
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Microscopy, Confocal
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Molecular Sequence Data
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Peptide Fragments / immunology*
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Receptors, Antigen, T-Cell / immunology*
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Saponins / pharmacology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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beta-Cyclodextrins*
Substances
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Antibodies, Monoclonal
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Antigens
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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B7-2 Antigen
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CD86 protein, human
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CDw78 antigen
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Cyclodextrins
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HLA-D Antigens
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HLA-DM antigens
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HLA-DP Antigens
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HLA-DR Antigens
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Histocompatibility Antigens Class II
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Lipopolysaccharides
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Macromolecular Substances
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Membrane Glycoproteins
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Membrane Proteins
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Saponins
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beta-Cyclodextrins
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invariant chain
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betadex