Abstract
NY-ESO-1-specific CD4(+) T cells are of interest for immune therapy against tumors, because it has been shown that their transfer into a patient with melanoma resulted in tumor regression. Therefore, we investigated how NY-ESO-1 is processed onto MHC class II molecules for direct CD4(+) T cell recognition of melanoma cells. We could rule out proteasome and autophagy-dependent endogenous Ag processing for MHC class II presentation. In contrast, intercellular Ag transfer, followed by classical MHC class II Ag processing via endocytosis, sensitized neighboring melanoma cells for CD4(+) T cell recognition. However, macroautophagy targeting of NY-ESO-1 enhanced MHC class II presentation. Therefore, both elevated NY-ESO-1 release and macroautophagy targeting could improve melanoma cell recognition by CD4(+) T cells and should be explored during immunotherapy of melanoma.
Copyright © 2015 by The American Association of Immunologists, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / analogs & derivatives
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Acetylcysteine / pharmacology
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Antigen Presentation / immunology
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Antigens, Neoplasm / immunology*
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Autophagy / immunology
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Autophagy-Related Protein 12
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / transplantation*
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Cell Line, Tumor
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Chloroquine / pharmacology
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Dendritic Cells / immunology
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Endocytosis / immunology
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Epitopes, T-Lymphocyte / immunology
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Histocompatibility Antigens Class II / immunology
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Humans
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Immunotherapy, Adoptive*
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Leupeptins
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Lymphocyte Activation / immunology
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Lysosomal-Associated Membrane Protein 2 / genetics
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Melanoma / immunology*
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Melanoma / therapy*
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Membrane Proteins / immunology*
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RNA Interference
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RNA, Small Interfering
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Small Ubiquitin-Related Modifier Proteins / genetics
Substances
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ATG12 protein, human
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Antigens, Neoplasm
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Autophagy-Related Protein 12
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CTAG1B protein, human
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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LAMP2 protein, human
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Leupeptins
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Lysosomal-Associated Membrane Protein 2
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Membrane Proteins
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RNA, Small Interfering
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Small Ubiquitin-Related Modifier Proteins
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lactacystin
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Chloroquine
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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Acetylcysteine