A large fraction of HLA class I ligands are proteasome-generated spliced peptides
The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8⁺ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced pepti...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2016-10, Vol.354 (6310), p.354-358 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Liepe, Juliane Marino, Fabio Sidney, John Jeko, Anita Bunting, Daniel E. Sette, Alessandro Kloetzel, Peter M. Stumpf, Michael P. H. Heck, Albert J. R. Mishto, Michele |
| description | The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8⁺ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy. |
| doi_str_mv | 10.1126/science.aaf4384 |
| format | Article |
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The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aaf4384</identifier><identifier>PMID: 27846572</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Abundance ; Antigen Presentation ; Antigens ; Cancer ; CD8-Positive T-Lymphocytes - immunology ; Cell Line, Tumor ; Computational Biology ; Epitopes, T-Lymphocyte - metabolism ; Histocompatibility Antigens Class I - metabolism ; Humans ; Immunology ; Ligands ; Lymphocytes ; Peptides ; Peptides - immunology ; Peptides - metabolism ; Pools ; Proteasome Endopeptidase Complex - metabolism ; Protein Splicing ; Vaccines</subject><ispartof>Science (American Association for the Advancement of Science), 2016-10, Vol.354 (6310), p.354-358</ispartof><rights>Copyright © 2016 American Association for the Advancement of Science</rights><rights>Copyright © 2016, American Association for the Advancement of Science.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-f04ebc056265db897a66aa01030ec1239ec66193faf5c060f77f0d1df4b441633</citedby><cites>FETCH-LOGICAL-c496t-f04ebc056265db897a66aa01030ec1239ec66193faf5c060f77f0d1df4b441633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/44710848$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/44710848$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27846572$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liepe, Juliane</creatorcontrib><creatorcontrib>Marino, Fabio</creatorcontrib><creatorcontrib>Sidney, John</creatorcontrib><creatorcontrib>Jeko, Anita</creatorcontrib><creatorcontrib>Bunting, Daniel E.</creatorcontrib><creatorcontrib>Sette, Alessandro</creatorcontrib><creatorcontrib>Kloetzel, Peter M.</creatorcontrib><creatorcontrib>Stumpf, Michael P. H.</creatorcontrib><creatorcontrib>Heck, Albert J. R.</creatorcontrib><creatorcontrib>Mishto, Michele</creatorcontrib><title>A large fraction of HLA class I ligands are proteasome-generated spliced peptides</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8⁺ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.</description><subject>Abundance</subject><subject>Antigen Presentation</subject><subject>Antigens</subject><subject>Cancer</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Line, Tumor</subject><subject>Computational Biology</subject><subject>Epitopes, T-Lymphocyte - metabolism</subject><subject>Histocompatibility Antigens Class I - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Peptides</subject><subject>Peptides - immunology</subject><subject>Peptides - metabolism</subject><subject>Pools</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein Splicing</subject><subject>Vaccines</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkDtPwzAUhS0EoqUwM4E8sqS9jp8ZqwpopUoICebIca6rVHlhpwP_nlQtzExnON89uvoIuWcwZyxVi-gqbB3OrfWCG3FBpgwymWQp8EsyBeAqMaDlhNzEuAcYu4xfk0mqjVBSp1PyvqS1DTukPlg3VF1LO0_X2yV1tY2Rbmhd7WxbRmoD0j50A9rYNZjssMVgByxp7OvKjdljP1Qlxlty5W0d8e6cM_L58vyxWifbt9fNarlNnMjUkHgQWDiQKlWyLEymrVLWAgMO6FjKM3RKsYx766UDBV5rDyUrvSiEYIrzGXk67Y5ffR0wDnlTRYd1bVvsDjFnRgnJTab0P1DBGBdaHlcXJ9SFLsaAPu9D1djwnTPIj8rzs_L8rHy8eDyPH4oGyz_-1_EIPJyAfRy68NcLoRkYYfgPd0aHUw</recordid><startdate>20161021</startdate><enddate>20161021</enddate><creator>Liepe, Juliane</creator><creator>Marino, Fabio</creator><creator>Sidney, John</creator><creator>Jeko, Anita</creator><creator>Bunting, Daniel E.</creator><creator>Sette, Alessandro</creator><creator>Kloetzel, Peter M.</creator><creator>Stumpf, Michael P. H.</creator><creator>Heck, Albert J. R.</creator><creator>Mishto, Michele</creator><general>American Association for the Advancement of Science</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>7U5</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>L7M</scope></search><sort><creationdate>20161021</creationdate><title>A large fraction of HLA class I ligands are proteasome-generated spliced peptides</title><author>Liepe, Juliane ; Marino, Fabio ; Sidney, John ; Jeko, Anita ; Bunting, Daniel E. ; Sette, Alessandro ; Kloetzel, Peter M. ; Stumpf, Michael P. H. ; Heck, Albert J. 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H.</au><au>Heck, Albert J. R.</au><au>Mishto, Michele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A large fraction of HLA class I ligands are proteasome-generated spliced peptides</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2016-10-21</date><risdate>2016</risdate><volume>354</volume><issue>6310</issue><spage>354</spage><epage>358</epage><pages>354-358</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><abstract>The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8⁺ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features. We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>27846572</pmid><doi>10.1126/science.aaf4384</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Abundance Antigen Presentation Antigens Cancer CD8-Positive T-Lymphocytes - immunology Cell Line, Tumor Computational Biology Epitopes, T-Lymphocyte - metabolism Histocompatibility Antigens Class I - metabolism Humans Immunology Ligands Lymphocytes Peptides Peptides - immunology Peptides - metabolism Pools Proteasome Endopeptidase Complex - metabolism Protein Splicing Vaccines |
| title | A large fraction of HLA class I ligands are proteasome-generated spliced peptides |
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