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dc.contributor.authorChen, Alex T.
dc.contributor.authorCornberg, Markus
dc.contributor.authorGras, Stephanie
dc.contributor.authorGuillonneau, Carole
dc.contributor.authorRossjohn, Jamie
dc.contributor.authorTrees, Andrew
dc.contributor.authorEmonet, Sebastien
dc.contributor.authorde la Torre, Juan C.
dc.contributor.authorWelsh, Raymond M.
dc.contributor.authorSelin, Liisa K.
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:47Z
dc.date.available2022-08-23T16:39:47Z
dc.date.issued2012-04-19
dc.date.submitted2012-09-06
dc.identifier.citationChen AT, Cornberg M, Gras S, Guillonneau C, Rossjohn J, et al. (2012) Loss of Anti-Viral Immunity by Infection with a Virus Encoding a Cross-Reactive Pathogenic Epitope. PLoS Pathog 8(4): e1002633. doi:10.1371/journal.ppat.1002633. <a href="http://dx.doi.org/10.1371/journal.ppat.1002633" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1002633
dc.identifier.pmid22536152
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39546
dc.description.abstractT cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. We questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive T cell epitope would affect protective immunity to a previously encountered virus. Pichinde virus (PV) and lymphocytic choriomeningitis virus (LCMV) encode subdominant cross-reactive NP(2)(0)(5)(-)(2)(1)(2) CD8 T cell epitopes sharing 6 of 8 amino acids, differing only in the MHC anchoring regions. These pMHC epitopes induce cross-reactive but non-identical T cell receptor (TCR) repertoires, and structural studies showed that the differing anchoring amino acids altered the conformation of the MHC landscape presented to the TCR. PV-immune mice receiving an intervening infection with wild type but not NP205-mutant LCMV developed severe immunopathology in the form of acute fatty necrosis on re-challenge with PV, and this pathology could be predicted by the ratio of NP205-specific to the normally immunodominant PV NP(3)(8)(-)(4)(5)-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22536152&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright: © 2012 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subjectAnimals
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCross Reactions
dc.subjectEpitopes, T-Lymphocyte
dc.subjectLymphocytic Choriomeningitis
dc.subjectLymphocytic choriomeningitis virus
dc.subjectMale
dc.subjectMice
dc.subjectMutation
dc.subjectPichinde virus
dc.subjectReceptors, Antigen, T-Cell
dc.subjectViral Proteins
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleLoss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume8
dc.source.issue4
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3340&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2340
dc.identifier.contextkey3299934
refterms.dateFOA2022-08-23T16:39:47Z
html.description.abstract<p>T cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. We questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive T cell epitope would affect protective immunity to a previously encountered virus. Pichinde virus (PV) and lymphocytic choriomeningitis virus (LCMV) encode subdominant cross-reactive NP(2)(0)(5)(-)(2)(1)(2) CD8 T cell epitopes sharing 6 of 8 amino acids, differing only in the MHC anchoring regions. These pMHC epitopes induce cross-reactive but non-identical T cell receptor (TCR) repertoires, and structural studies showed that the differing anchoring amino acids altered the conformation of the MHC landscape presented to the TCR. PV-immune mice receiving an intervening infection with wild type but not NP205-mutant LCMV developed severe immunopathology in the form of acute fatty necrosis on re-challenge with PV, and this pathology could be predicted by the ratio of NP205-specific to the normally immunodominant PV NP(3)(8)(-)(4)(5)-specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses.</p>
dc.identifier.submissionpathoapubs/2340
dc.contributor.departmentDepartment of Pathology
dc.source.pagese1002633


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