Abstract
The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii(-/-) mice. Downregulation reflects an increased rate of degradation in Ii(-/-) cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, Differentiation, B-Lymphocyte / biosynthesis
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Antigens, Differentiation, B-Lymphocyte / physiology*
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Cells, Cultured
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Chemical Precipitation
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Cytosol / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Endopeptidases / metabolism*
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Endoplasmic Reticulum / immunology
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Endoplasmic Reticulum / metabolism
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HLA-D Antigens / genetics
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HLA-D Antigens / isolation & purification
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HLA-D Antigens / metabolism*
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Half-Life
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Histocompatibility Antigens Class II / biosynthesis
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / metabolism
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Histocompatibility Antigens Class II / physiology*
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Hydrolysis
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Folding
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RNA, Messenger / metabolism
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Spleen / cytology
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Spleen / immunology*
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Spleen / metabolism*
Substances
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Antigens, Differentiation, B-Lymphocyte
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H2-M antigens
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HLA-D Antigens
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HLA-DM antigens
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Histocompatibility Antigens Class II
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RNA, Messenger
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invariant chain
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Endopeptidases