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dc.contributor.authorYork, Ian A.
dc.contributor.authorBrehm, Michael A.
dc.contributor.authorZendzian, Sophia
dc.contributor.authorTowne, Charles Fenton
dc.contributor.authorRock, Kenneth L.
dc.date2022-08-11T08:09:36.000
dc.date.accessioned2022-08-23T16:37:00Z
dc.date.available2022-08-23T16:37:00Z
dc.date.issued2006-06-07
dc.date.submitted2009-04-02
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9202-7. Epub 2006 Jun 5. <a href="http://dx.doi.org/10.1073/pnas.0603095103">Link to article on publisher's site</a></p>
dc.identifier.issn0027-8424 (Print)
dc.identifier.doi10.1073/pnas.0603095103
dc.identifier.pmid16754858
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38916
dc.description.abstractCD8(+) T cells respond to short peptides bound to MHC class I molecules. Although most antigenic proteins contain many sequences that could bind to MHC class I, few of these peptides actually stimulate CD8(+) T cell responses. Moreover, the T cell responses that are generated often follow a very reproducible hierarchy to different peptides for reasons that are poorly understood. We find that the loss of a single enzyme, endoplasmic reticulum aminopeptidase 1 (ERAP1), in the antigen-processing pathway results in a marked shift in the hierarchy of immunodominance in viral infections, even when the responding T cells have the same T cell receptor repertoire. In mice, ERAP1 is the major enzyme that trims precursor peptides in the endoplasmic reticulum and, in this process, can generate or destroy antigenic peptides. Consequently, when ERAP1 is lost, the immune response to some viral peptides is reduced, to others increased, and to yet others unchanged. Therefore, many epitopes must be initially generated as precursors that are normally trimmed by ERAP1 before binding to MHC class I, whereas others are normally degraded by ERAP1 to lengths that are too short to bind to MHC class I. Moreover, peptide trimming and the resulting abundance of peptide-MHC complexes are dominant factors in establishing immunodominance.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16754858&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1482590/
dc.subjectAdoptive Transfer
dc.subjectAmino Acid Sequence
dc.subjectAminopeptidases
dc.subjectAnimals
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCells, Cultured
dc.subjectEpitopes
dc.subjectFibroblasts
dc.subject*Genes, MHC Class I
dc.subjectImmune System
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectPeptides
dc.subjectSpleen
dc.subjectViruses
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleEndoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume103
dc.source.issue24
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1749
dc.identifier.contextkey808514
html.description.abstract<p>CD8(+) T cells respond to short peptides bound to MHC class I molecules. Although most antigenic proteins contain many sequences that could bind to MHC class I, few of these peptides actually stimulate CD8(+) T cell responses. Moreover, the T cell responses that are generated often follow a very reproducible hierarchy to different peptides for reasons that are poorly understood. We find that the loss of a single enzyme, endoplasmic reticulum aminopeptidase 1 (ERAP1), in the antigen-processing pathway results in a marked shift in the hierarchy of immunodominance in viral infections, even when the responding T cells have the same T cell receptor repertoire. In mice, ERAP1 is the major enzyme that trims precursor peptides in the endoplasmic reticulum and, in this process, can generate or destroy antigenic peptides. Consequently, when ERAP1 is lost, the immune response to some viral peptides is reduced, to others increased, and to yet others unchanged. Therefore, many epitopes must be initially generated as precursors that are normally trimmed by ERAP1 before binding to MHC class I, whereas others are normally degraded by ERAP1 to lengths that are too short to bind to MHC class I. Moreover, peptide trimming and the resulting abundance of peptide-MHC complexes are dominant factors in establishing immunodominance.</p>
dc.identifier.submissionpathoapubs/1749
dc.contributor.departmentDepartment of Pathology
dc.source.pages9202-7


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