Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes.
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 prote...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1999
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| _version_ | 1826259620491952128 |
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| author | Gileadi, U Gallimore, A Van der Bruggen, P Cerundolo, V |
| author_facet | Gileadi, U Gallimore, A Van der Bruggen, P Cerundolo, V |
| author_sort | Gileadi, U |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:52:45Z |
| format | Journal article |
| id | oxford-uuid:10cd4c23-3904-4abd-b83e-7f04373009e4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:52:45Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:10cd4c23-3904-4abd-b83e-7f04373009e42022-03-26T09:58:28ZEffect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:10cd4c23-3904-4abd-b83e-7f04373009e4EnglishSymplectic Elements at Oxford1999Gileadi, UGallimore, AVan der Bruggen, PCerundolo, VWe 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. |
| spellingShingle | Gileadi, U Gallimore, A Van der Bruggen, P Cerundolo, V Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title | Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title_full | Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title_fullStr | Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title_full_unstemmed | Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title_short | Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. |
| title_sort | effect of epitope flanking residues on the presentation of n terminal cytotoxic t lymphocyte epitopes |
| work_keys_str_mv | AT gileadiu effectofepitopeflankingresiduesonthepresentationofnterminalcytotoxictlymphocyteepitopes AT gallimorea effectofepitopeflankingresiduesonthepresentationofnterminalcytotoxictlymphocyteepitopes AT vanderbruggenp effectofepitopeflankingresiduesonthepresentationofnterminalcytotoxictlymphocyteepitopes AT cerundolov effectofepitopeflankingresiduesonthepresentationofnterminalcytotoxictlymphocyteepitopes |