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-K-k and H2-D-b 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.