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We here demonstrate that placing two distinct influenza virus nucleoprotein epitopes at the N terminus of a cytosolic protein selectively blocks their presentation to specific cytotoxic T lymphocytes. The block is a cytosolic phenomenon, which can be overcome by distancing the epitope from the protein N terminus by two or more amino acids. Shortening the protein's C terminus fails to relieve the antigen presentation block. These results demonstrate that events at the N terminus of the target protein, rather than at its C terminus, are responsible for the lack of presentation of N-terminal epitopes. We also show that lack of presentation of N terminal epitopes is associated with a modification of the target protein which affects its electrophoretic mobility and isoelectric focusing point. This modification can be prevented by mutating the epitope's N-terminal flanking sequence, which results in an efficient presentation of the N-terminal epitope. Lack of presentation of the N-terminal epitopes results in a reduced ability of influenza-primed mice to clear acute infection with vaccinia virus encoding an N-terminal nucleoprotein epitope. Our results demonstrate that presentation of epitopes localized at the N terminus of cytosolic proteins can be modulated by events occurring at early stages of antigen processing.

Original publication

DOI

10.1002/(SICI)1521-4141(199907)29:07<2213::AID-IMMU2213>3.0.CO;2-8

Type

Journal article

Journal

Eur J Immunol

Publication Date

07/1999

Volume

29

Pages

2213 - 2222

Keywords

Animals, Antigen Presentation, Antigens, Base Sequence, Cell Line, DNA Primers, Electrophoresis, Polyacrylamide Gel, Epitopes, Female, Mice, Mice, Inbred C57BL, Mutation, T-Lymphocytes, Cytotoxic, Vaccinia virus