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The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide
The 20S proteasome is involved in the processing of MHC class I-presented Ags. A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing a...
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Published in: | The Journal of immunology (1950) 2001-08, Vol.167 (3), p.1515-1521 |
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container_title | The Journal of immunology (1950) |
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creator | Knuehl, Christine Spee, Pieter Ruppert, Thomas Kuckelkorn, Ulrike Henklein, Peter Neefjes, Jacques Kloetzel, Peter-M |
description | The 20S proteasome is involved in the processing of MHC class I-presented Ags. A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing and TAP-dependent ER translocation of the immunodominant epitope of the murine CMV immediate early protein pp89. For the first time, we experimentally linked peptide generation by the proteasome system and TAP-dependent ER translocation. Our experiments show that the proteasome generates both an N-terminally extended 11-mer precursor peptide as well as the correct H2-L(d) 9-mer epitope, a process that is accelerated in the presence of PA28. Our direct peptide translocation assays, however, demonstrate that only the 11-mer precursor peptide is transported into the ER by TAPs, whereas the epitope itself is not translocated. In consequence, our combined proteasome/TAP assays show that the 11-mer precursor is the immunorelevant peptide product that requires N-terminal trimming in the ER for MHC class I binding. |
doi_str_mv | 10.4049/jimmunol.167.3.1515 |
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A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing and TAP-dependent ER translocation of the immunodominant epitope of the murine CMV immediate early protein pp89. For the first time, we experimentally linked peptide generation by the proteasome system and TAP-dependent ER translocation. Our experiments show that the proteasome generates both an N-terminally extended 11-mer precursor peptide as well as the correct H2-L(d) 9-mer epitope, a process that is accelerated in the presence of PA28. Our direct peptide translocation assays, however, demonstrate that only the 11-mer precursor peptide is transported into the ER by TAPs, whereas the epitope itself is not translocated. 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A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing and TAP-dependent ER translocation of the immunodominant epitope of the murine CMV immediate early protein pp89. For the first time, we experimentally linked peptide generation by the proteasome system and TAP-dependent ER translocation. Our experiments show that the proteasome generates both an N-terminally extended 11-mer precursor peptide as well as the correct H2-L(d) 9-mer epitope, a process that is accelerated in the presence of PA28. Our direct peptide translocation assays, however, demonstrate that only the 11-mer precursor peptide is transported into the ER by TAPs, whereas the epitope itself is not translocated. In consequence, our combined proteasome/TAP assays show that the 11-mer precursor is the immunorelevant peptide product that requires N-terminal trimming in the ER for MHC class I binding.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antigen Presentation</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 2</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 3</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Autoantigens</subject><subject>Biological Transport, Active - immunology</subject><subject>Cell Line</subject><subject>Cysteine Endopeptidases - metabolism</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Endoplasmic Reticulum - immunology</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>H-2 Antigens - biosynthesis</subject><subject>H-2 Antigens - metabolism</subject><subject>Histocompatibility Antigen H-2D</subject><subject>Humans</subject><subject>Immediate-Early Proteins - biosynthesis</subject><subject>Immediate-Early Proteins - metabolism</subject><subject>Immunodominant Epitopes - biosynthesis</subject><subject>Immunodominant Epitopes - metabolism</subject><subject>Mice</subject><subject>Microsomes - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Molecular Weight</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Muromegalovirus - immunology</subject><subject>Muscle Proteins</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - metabolism</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Protein Precursors - biosynthesis</subject><subject>Protein Precursors - chemical synthesis</subject><subject>Protein Precursors - metabolism</subject><subject>Proteins - pharmacology</subject><subject>Rats</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpNkU1vEzEQhi0EoqHwC5CQT3Da4PHGdvaIqtBGSgVC4Ww59qRx5Y_F3m3Uf8LPZdsEwWlGo-d95_AQ8h7YfMEW3ed7H-OYcpiDVPN2DgLECzIDIVgjJZMvyYwxzhtQUl2QN7XeM8Yk44vX5AJgIWWr-Iz83h6Q3o7FJ6RXj0OOeGdCfvBlrLTvlx1dPz9xOfpk0kBvGr5xdNX7IfdI15VeY8JiBnTUJEe3xaQasn0--DRkOkz9q-RyH0yN3tIfOHg7hjFSU6cIBWhusdDvBe1Yap427Afv8C15tTeh4rvzvCQ_v662VzfN5tv1-urLprGcC9EAF8tOyk4A59ZIrqxg0jqGTinFjJXgBDq-50YawCVwKZzDjgNndqd2tr0kH0-9fcm_RqyDjr5aDMEkzGPVChjvoOUT2J5AW3KtBfe6Lz6a8qiB6Sch-q8QPQnRrX4SMqU-nOvHXUT3L3M2MAGfTsDB3x2OvqCu0YQw4aCPx-N_VX8ADFeX1w</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>Knuehl, Christine</creator><creator>Spee, Pieter</creator><creator>Ruppert, Thomas</creator><creator>Kuckelkorn, Ulrike</creator><creator>Henklein, Peter</creator><creator>Neefjes, Jacques</creator><creator>Kloetzel, Peter-M</creator><general>Am Assoc Immnol</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></search><sort><creationdate>20010801</creationdate><title>The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide</title><author>Knuehl, Christine ; Spee, Pieter ; Ruppert, Thomas ; Kuckelkorn, Ulrike ; Henklein, Peter ; Neefjes, Jacques ; Kloetzel, Peter-M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2255-125896695122ca627c506cd0ed7770ac61d5ed2f2a6a1e81265dde92120cb7bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antigen Presentation</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 2</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 3</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Autoantigens</topic><topic>Biological Transport, Active - immunology</topic><topic>Cell Line</topic><topic>Cysteine Endopeptidases - metabolism</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Endoplasmic Reticulum - immunology</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>H-2 Antigens - biosynthesis</topic><topic>H-2 Antigens - metabolism</topic><topic>Histocompatibility Antigen H-2D</topic><topic>Humans</topic><topic>Immediate-Early Proteins - biosynthesis</topic><topic>Immediate-Early Proteins - metabolism</topic><topic>Immunodominant Epitopes - biosynthesis</topic><topic>Immunodominant Epitopes - metabolism</topic><topic>Mice</topic><topic>Microsomes - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Molecular Weight</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Muromegalovirus - immunology</topic><topic>Muscle Proteins</topic><topic>Peptides - chemical synthesis</topic><topic>Peptides - metabolism</topic><topic>Proteasome Endopeptidase Complex</topic><topic>Protein Precursors - biosynthesis</topic><topic>Protein Precursors - chemical synthesis</topic><topic>Protein Precursors - metabolism</topic><topic>Proteins - pharmacology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knuehl, Christine</creatorcontrib><creatorcontrib>Spee, Pieter</creatorcontrib><creatorcontrib>Ruppert, Thomas</creatorcontrib><creatorcontrib>Kuckelkorn, Ulrike</creatorcontrib><creatorcontrib>Henklein, Peter</creatorcontrib><creatorcontrib>Neefjes, Jacques</creatorcontrib><creatorcontrib>Kloetzel, Peter-M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knuehl, Christine</au><au>Spee, Pieter</au><au>Ruppert, Thomas</au><au>Kuckelkorn, Ulrike</au><au>Henklein, Peter</au><au>Neefjes, Jacques</au><au>Kloetzel, Peter-M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>167</volume><issue>3</issue><spage>1515</spage><epage>1521</epage><pages>1515-1521</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The 20S proteasome is involved in the processing of MHC class I-presented Ags. A number of epitopes is known to be generated as precursor peptides requiring trimming either before or after translocation into the endoplasmic reticulum (ER). In this study, we have followed the proteasomal processing and TAP-dependent ER translocation of the immunodominant epitope of the murine CMV immediate early protein pp89. For the first time, we experimentally linked peptide generation by the proteasome system and TAP-dependent ER translocation. Our experiments show that the proteasome generates both an N-terminally extended 11-mer precursor peptide as well as the correct H2-L(d) 9-mer epitope, a process that is accelerated in the presence of PA28. Our direct peptide translocation assays, however, demonstrate that only the 11-mer precursor peptide is transported into the ER by TAPs, whereas the epitope itself is not translocated. In consequence, our combined proteasome/TAP assays show that the 11-mer precursor is the immunorelevant peptide product that requires N-terminal trimming in the ER for MHC class I binding.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11466372</pmid><doi>10.4049/jimmunol.167.3.1515</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Antigen Presentation ATP Binding Cassette Transporter, Subfamily B, Member 2 ATP Binding Cassette Transporter, Subfamily B, Member 3 ATP-Binding Cassette Transporters - metabolism Autoantigens Biological Transport, Active - immunology Cell Line Cysteine Endopeptidases - metabolism Endoplasmic Reticulum - enzymology Endoplasmic Reticulum - immunology Endoplasmic Reticulum - metabolism H-2 Antigens - biosynthesis H-2 Antigens - metabolism Histocompatibility Antigen H-2D Humans Immediate-Early Proteins - biosynthesis Immediate-Early Proteins - metabolism Immunodominant Epitopes - biosynthesis Immunodominant Epitopes - metabolism Mice Microsomes - metabolism Molecular Sequence Data Molecular Weight Multienzyme Complexes - metabolism Muromegalovirus - immunology Muscle Proteins Peptides - chemical synthesis Peptides - metabolism Proteasome Endopeptidase Complex Protein Precursors - biosynthesis Protein Precursors - chemical synthesis Protein Precursors - metabolism Proteins - pharmacology Rats |
title | The Murine Cytomegalovirus pp89 Immunodominant H-2Ld Epitope Is Generated and Translocated into the Endoplasmic Reticulum as an 11-Mer Precursor Peptide |
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