Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes.

Journal article

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.

Authors: Gileadi, U; Gallimore, A; Van der Bruggen, P; Cerundolo, V

• Publication status: Published
• Journal: European journal of immunology
• Volume: 29
• Issue: 7
• Pages: 2213-2222
• Publication date: 1999-07-01
• DOI: 10.1002/(sici)1521-4141(199907)29:07<2213::aid-immu2213>3.0.co;2-8
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Mice, Inbred C57BL; Electrophoresis, Polyacrylamide Gel; Antigen Presentation; Animals; DNA Primers; Epitopes; Mice; Antigens; Mutation; Cell Line; Vaccinia virus; T-Lymphocytes, Cytotoxic; Female; Base Sequence