Glycan-regulated antigen processing of a protein in the endoplasmic reticulum can uncover cryptic cytotoxic T cell epitopes.
We and others have shown that influenza A nucleoprotein (NP) targeted to the secretory pathway cannot be processed to yield several cytotoxic T lymphocyte (CTL) epitopes in cell lines that lack the transporter associated with antigen processing (TAP). However, a large COOH-terminal fragment of NP is processed and presented in these cells. Full-length NP is cotranslationally glycosylated in the lumen of the endoplasmic reticulum at two sites distal to the major H2-Kk and H2-Db restricted CTL epitopes, and we show here that pharmacological or genetic inhibition of N-linked glycosylation, leads to the processing and presentation of both these epitopes in a TAP-independent way.
Institute for Molecular Medicine and Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
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D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D019556:COS Cells; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D011134:Polysaccharides / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D011134:Polysaccharides; D011506:Proteins