Abstract
N-linked glycans are thought to protect class II major histocompatibility complex (MHC) molecules (MHCII) from proteolytic cleavage and assist in arranging proteins within the immune synapse, but were not thought to directly participate in antigen presentation. Here, we report that antigen-presenting cells (APCs) lacking native complex N-glycans showed reduced MHCII binding and presentation of the T cell activating glycoantigen (GlyAg) polysaccharide A from Bacteroides fragilis but not conventional peptides. APCs lacking native N-glycans also failed to mediate GlyAg-driven T cell activation but activated T cells normally with protein antigen. Mice treated with the mannosidase inhibitor kifunensine to prevent the formation of complex N-glycans were unable to expand GlyAg-specific T cells in vivo upon immunization, yet adoptive transfer of normally glycosylated APCs into these animals overcame this defect. Our findings reveal that MHCII N-glycosylation directly impacts binding and presentation of at least one class of T cell-dependent antigen.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkaloids / pharmacology
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Animals
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Antigen Presentation / drug effects
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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Antigen-Presenting Cells / immunology*
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Antigen-Presenting Cells / metabolism
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology*
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Antigens, Bacterial / metabolism
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Bacteroides fragilis / genetics
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Bacteroides fragilis / immunology*
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Bacteroides fragilis / metabolism
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Glycosylation
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HEK293 Cells
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism
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Humans
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mannosidases / antagonists & inhibitors
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Mannosidases / genetics
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Mannosidases / immunology
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Mannosidases / metabolism
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Mice
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Polysaccharides, Bacterial / genetics
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Polysaccharides, Bacterial / immunology*
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Polysaccharides, Bacterial / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Alkaloids
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Antigens, Bacterial
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Histocompatibility Antigens Class II
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Polysaccharides, Bacterial
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kifunensine
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Mannosidases