In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expressi...
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| Veröffentlicht in: | The Journal of experimental medicine 2006-03, Vol.203 (3), p.647-659 |
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| container_title | The Journal of experimental medicine |
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| creator | Yan, Jingbo Parekh, Vrajesh V Mendez-Fernandez, Yanice Olivares-Villagómez, Danyvid Dragovic, Srdjan Hill, Timothy Roopenian, Derry C Joyce, Sebastian Van Kaer, Luc |
| description | Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b-restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I-presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. |
| doi_str_mv | 10.1084/jem.20052271 |
| format | Article |
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To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b-restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I-presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>EISSN: 1892-1007</identifier><identifier>DOI: 10.1084/jem.20052271</identifier><identifier>PMID: 16505142</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Aminopeptidases - deficiency ; Aminopeptidases - immunology ; Animals ; Antigen Presentation - genetics ; Antigen Presentation - immunology ; CD8-Positive T-Lymphocytes - immunology ; Gene Expression Regulation - genetics ; Gene Expression Regulation - immunology ; H-2 Antigens - immunology ; Histocompatibility Antigens Class I - immunology ; Mice ; Mice, Knockout ; Minor Histocompatibility Antigens ; Peptides - immunology</subject><ispartof>The Journal of experimental medicine, 2006-03, Vol.203 (3), p.647-659</ispartof><rights>Copyright © 2006, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-581ec3df833065586015eafb4a375b938100f25e4a40a7928b586489129dabc3</citedby><cites>FETCH-LOGICAL-c479t-581ec3df833065586015eafb4a375b938100f25e4a40a7928b586489129dabc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16505142$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Jingbo</creatorcontrib><creatorcontrib>Parekh, Vrajesh V</creatorcontrib><creatorcontrib>Mendez-Fernandez, Yanice</creatorcontrib><creatorcontrib>Olivares-Villagómez, Danyvid</creatorcontrib><creatorcontrib>Dragovic, Srdjan</creatorcontrib><creatorcontrib>Hill, Timothy</creatorcontrib><creatorcontrib>Roopenian, Derry C</creatorcontrib><creatorcontrib>Joyce, Sebastian</creatorcontrib><creatorcontrib>Van Kaer, Luc</creatorcontrib><title>In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b-restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I-presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.</description><subject>Aminopeptidases - deficiency</subject><subject>Aminopeptidases - immunology</subject><subject>Animals</subject><subject>Antigen Presentation - genetics</subject><subject>Antigen Presentation - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Gene Expression Regulation - genetics</subject><subject>Gene Expression Regulation - immunology</subject><subject>H-2 Antigens - immunology</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Minor Histocompatibility Antigens</subject><subject>Peptides - immunology</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1892-1007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1r3DAQxUVpaTZpbzkHnXqqU31a8qUQljRZSCmU3MVYHqcKtuVK2oW99G-vQzZJc-ppGN6PN_N4hJxyds6ZVV_ucTwXjGkhDH9DVlwrVjVa2rdkxZgQFWfMHJHjnO8Z40rp-j054rVmmiuxIn82E92FXaQpDkhjTy9_VpBz9AEKdnTGuYQOMlLwJexC2dMw0QJhiClMdwcdM-1jonPCjFOBEuJE2z39fr2mfljc6AYoTN3T0tJxOea3A-YP5F0PQ8aPh3lCbr9d3q6vq5sfV5v1xU3llWlKpS1HL7veSslqrW3NuEboWwXS6LaRdgnZC40KFAPTCNsujLINF00HrZcn5Ouj7bxtR-z88mWCwc0pjJD2LkJwr5Up_HJ3cecE51ZovRh8Ohik-HuLubgxZI_DABPGbXa1MYZJq_4LcsO5kuYB_PwI-hRzTtg_f8OZeyjWLcW6p2IX_OzfBC_woUn5F2Cjn8g</recordid><startdate>20060320</startdate><enddate>20060320</enddate><creator>Yan, Jingbo</creator><creator>Parekh, Vrajesh V</creator><creator>Mendez-Fernandez, Yanice</creator><creator>Olivares-Villagómez, Danyvid</creator><creator>Dragovic, Srdjan</creator><creator>Hill, Timothy</creator><creator>Roopenian, Derry C</creator><creator>Joyce, Sebastian</creator><creator>Van Kaer, Luc</creator><general>The Rockefeller University Press</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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060320</creationdate><title>In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules</title><author>Yan, Jingbo ; 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Aminopeptidases - deficiency Aminopeptidases - immunology Animals Antigen Presentation - genetics Antigen Presentation - immunology CD8-Positive T-Lymphocytes - immunology Gene Expression Regulation - genetics Gene Expression Regulation - immunology H-2 Antigens - immunology Histocompatibility Antigens Class I - immunology Mice Mice, Knockout Minor Histocompatibility Antigens Peptides - immunology |
| title | In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules |
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