Abstract
Efficient loading of major histocompatibility complex class II molecules with peptides requires the invariant chain (Ii) and the class II-like molecule H-2M. Recent in vitro biochemical studies suggest that H2-M may function as a chaperone to rescue empty class II dimers. To test this hypothesis in vivo, we generated mice lacking both Ii and H-2M (Ii-/-M-/-). Antigen presenting cells (APCs) from Ii-/-M-/- mice, as compared with APCs from Ii-/- mice, exhibit a significant reduction in their ability to present self-peptides to a panel of class II I-Ab-restricted T cells. As a consequence of this defect in the loading of self peptides, CD4(+) thymocyte development is profoundly impaired in Ii-/-M-/- mice, resulting in a peripheral CD4(+) T cell population with low levels of T cell receptor expression. These findings are consistent with the idea that H-2M functions as a chaperone in the peptide loading of class II molecules 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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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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Autoantigens / metabolism
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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H-2 Antigens / genetics*
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H-2 Antigens / physiology*
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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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Macromolecular Substances
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Peptides / immunology*
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Peptides / metabolism*
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Peptides / physiology
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Protein Binding / genetics
Substances
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Antigens, Differentiation, B-Lymphocyte
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Autoantigens
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H-2 Antigens
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Histocompatibility Antigens Class II
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Macromolecular Substances
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Peptides
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invariant chain