Abstract
Processing of proteins for major histocompatibility complex (MHC) class II-restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins frequently contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal thiol reductase (GILT) is constitutively present in late endocytic compartments of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to antigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact structure containing four disulfide bonds, was examined in detail.
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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Amino Acid Sequence
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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 / chemistry
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Antigens / immunology
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Antigens / metabolism
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Cell Line
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Dendritic Cells / enzymology
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Disulfides / chemistry
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Epitopes / immunology
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Epitopes / metabolism
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Hybridomas
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Hydrogen-Ion Concentration
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Immunization
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Muramidase / chemistry
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Muramidase / immunology*
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Muramidase / metabolism
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Oxidoreductases / chemistry
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Oxidoreductases / genetics
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Oxidoreductases / metabolism*
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Oxidoreductases Acting on Sulfur Group Donors
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Protein Conformation
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Protein Folding
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Spleen / immunology
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T-Lymphocytes / immunology*
Substances
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Antigens
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Disulfides
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Epitopes
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Histocompatibility Antigens Class II
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Oxidoreductases
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Ifi30 protein, mouse
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Oxidoreductases Acting on Sulfur Group Donors
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hen egg lysozyme
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Muramidase