Minimal Epitopes Expressed in a Recombinant Polyepitope Protein are Processed and Presented to CD8+Cytotoxic T Cells: Implications for Vaccine Design
The epitopes recognized by CD8+cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artific...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (13), p.5845-5849 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 92 |
| creator | Thomson, Scott A. Khanna, Rajiv Gardner, Joy Burrows, Scott R. Coupar, Barbara Moss, Denis J. Suhrbier, Andreas |
| description | The epitopes recognized by CD8+cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines. |
| doi_str_mv | 10.1073/pnas.92.13.5845 |
| format | Article |
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The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.13.5845</identifier><identifier>PMID: 7541138</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Antibodies ; Antigens, Viral - immunology ; Cell lines ; Clone Cells ; DNA ; DNA Primers ; DNA-Binding Proteins - immunology ; Drug Design ; Epitopes ; Epitopes - biosynthesis ; Epitopes - immunology ; Epstein Barr virus infections ; Epstein-Barr Virus Nuclear Antigens ; HLA Antigens - immunology ; HLA-A Antigens - immunology ; HLA-B Antigens - immunology ; Humans ; Molecular Sequence Data ; Oligonucleotides ; Polymerase Chain Reaction ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - immunology ; T lymphocytes ; T-Lymphocytes, Cytotoxic - immunology ; Vaccination ; Vaccines, Synthetic ; Vaccinia virus - immunology ; Viral Vaccines</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-06, Vol.92 (13), p.5845-5849</ispartof><rights>Copyright 1995 The National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-292d8034f4026525e0906a17321d52181b457bab25446e6cf5289e94dd6b0a373</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/13.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2367925$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2367925$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7541138$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thomson, Scott A.</creatorcontrib><creatorcontrib>Khanna, Rajiv</creatorcontrib><creatorcontrib>Gardner, Joy</creatorcontrib><creatorcontrib>Burrows, Scott R.</creatorcontrib><creatorcontrib>Coupar, Barbara</creatorcontrib><creatorcontrib>Moss, Denis J.</creatorcontrib><creatorcontrib>Suhrbier, Andreas</creatorcontrib><title>Minimal Epitopes Expressed in a Recombinant Polyepitope Protein are Processed and Presented to CD8+Cytotoxic T Cells: Implications for Vaccine Design</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The epitopes recognized by CD8+cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Antibodies</subject><subject>Antigens, Viral - immunology</subject><subject>Cell lines</subject><subject>Clone Cells</subject><subject>DNA</subject><subject>DNA Primers</subject><subject>DNA-Binding Proteins - immunology</subject><subject>Drug Design</subject><subject>Epitopes</subject><subject>Epitopes - biosynthesis</subject><subject>Epitopes - immunology</subject><subject>Epstein Barr virus infections</subject><subject>Epstein-Barr Virus Nuclear Antigens</subject><subject>HLA Antigens - immunology</subject><subject>HLA-A Antigens - immunology</subject><subject>HLA-B Antigens - immunology</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotides</subject><subject>Polymerase Chain Reaction</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - immunology</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Vaccination</subject><subject>Vaccines, Synthetic</subject><subject>Vaccinia virus - immunology</subject><subject>Viral Vaccines</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEKkNhzQaQV7BAmfo3sREblA5QqYgKFbaW4zjFVWIH24NmHoT3xSHDABtW9tX5zr3XPkXxGME1gjU5m5yKa4HXiKwZp-xOsUJQoLKiAt4tVhDiuuQU0_vFgxhvIYSCcXhSnNSMIkT4qvjxwTo7qgFsJpv8ZCLY7KZgYjQdsA4o8MloP7bWKZfAlR_2ZuHAVfDJzET4ddeLRbkuVyYal3KVPGjO-ctmn3zyO6vBNWjMMMRX4GKcBqtVst5F0PsAviitrTPg3ER74x4W93o1RPPocJ4Wn99urpv35eXHdxfNm8tS0wqnEgvccUhoTyGuGGYGClgpVBOMOoYRRy1ldatazCitTKV7hrkwgnZd1UJFanJavF76Ttt2NJ3Oawc1yCnkLwl76ZWV_yrOfpU3_rukiAme7c8P9uC_bU1McrRR5xcqZ_w2yromFa85zuDZAurgYwymP45AUM45yjlHKbBERM45ZsfTvzc78ofgsv7ioM_G3-qfBrLfDkMyu5TJZ_8lM_BkAW5j8uFIYFLVAjPyEz_TvQE</recordid><startdate>19950620</startdate><enddate>19950620</enddate><creator>Thomson, Scott A.</creator><creator>Khanna, Rajiv</creator><creator>Gardner, Joy</creator><creator>Burrows, Scott R.</creator><creator>Coupar, Barbara</creator><creator>Moss, Denis J.</creator><creator>Suhrbier, Andreas</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950620</creationdate><title>Minimal Epitopes Expressed in a Recombinant Polyepitope Protein are Processed and Presented to CD8+Cytotoxic T Cells: Implications for Vaccine Design</title><author>Thomson, Scott A. ; 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The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7541138</pmid><doi>10.1073/pnas.92.13.5845</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1995-06, Vol.92 (13), p.5845-5849 |
| issn | 0027-8424 1091-6490 |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Amino acids Antibodies Antigens, Viral - immunology Cell lines Clone Cells DNA DNA Primers DNA-Binding Proteins - immunology Drug Design Epitopes Epitopes - biosynthesis Epitopes - immunology Epstein Barr virus infections Epstein-Barr Virus Nuclear Antigens HLA Antigens - immunology HLA-A Antigens - immunology HLA-B Antigens - immunology Humans Molecular Sequence Data Oligonucleotides Polymerase Chain Reaction Recombinant Proteins - biosynthesis Recombinant Proteins - immunology T lymphocytes T-Lymphocytes, Cytotoxic - immunology Vaccination Vaccines, Synthetic Vaccinia virus - immunology Viral Vaccines |
| title | Minimal Epitopes Expressed in a Recombinant Polyepitope Protein are Processed and Presented to CD8+Cytotoxic T Cells: Implications for Vaccine Design |
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