Abstract
CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation*
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Autophagy*
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B-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / immunology
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Cell Line
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Cell Line, Transformed
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Cell Line, Tumor
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Chloroquine / pharmacology
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Epstein-Barr Virus Nuclear Antigens / immunology
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Epstein-Barr Virus Nuclear Antigens / metabolism*
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Histocompatibility Antigens Class II / metabolism*
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Humans
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Hydrogen-Ion Concentration
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Lysosomes / immunology
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Lysosomes / metabolism
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Microsomes / metabolism
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Phagosomes / immunology
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Phagosomes / metabolism*
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Phagosomes / ultrastructure
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Proteasome Endopeptidase Complex / metabolism
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Transfection
Substances
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Epstein-Barr Virus Nuclear Antigens
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Histocompatibility Antigens Class II
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Chloroquine
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Proteasome Endopeptidase Complex
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EBV-encoded nuclear antigen 1