Abstract
Degradation of invariant chain (Ii) is a critical step in major histocompatibility complex class II-restricted antigen presentation. Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)-derived antigen-presenting cells (APCs). Consequently, positive selection of CD4+ T cells was reduced. Because different cysteine proteinases are responsible for specific Ii degradation steps in cTECs and BM-derived APCs, the proteolytic environment in cells mediating positive and negative selection may be distinct. The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4+ T cell responsiveness in vivo.
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 Presentation*
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Antigen-Presenting Cells / enzymology
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Antigen-Presenting Cells / immunology
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Antigens, Differentiation, B-Lymphocyte / metabolism*
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Bone Marrow Cells / enzymology
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Bone Marrow Cells / immunology
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / enzymology
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / immunology
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Cathepsin L
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Cathepsins / genetics
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Cathepsins / metabolism*
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Cysteine Endopeptidases
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Endopeptidases*
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Epithelial Cells / enzymology
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Histocompatibility Antigens Class II / metabolism*
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Mice
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Mice, Inbred C57BL
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Mutation
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / immunology
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Thymus Gland / enzymology
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Thymus Gland / immunology*
Substances
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Antigens, Differentiation, B-Lymphocyte
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Histocompatibility Antigens Class II
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invariant chain
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Cathepsins
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Endopeptidases
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Cysteine Endopeptidases
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Cathepsin L
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Ctsl protein, mouse
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cathepsin S