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dc.contributor.authorBecerra Artiles, Aniuska
dc.contributor.authorCruz, John
dc.contributor.authorLeszyk, John D.
dc.contributor.authorSidney, John
dc.contributor.authorSette, Alessandro
dc.contributor.authorShaffer, Scott A.
dc.contributor.authorStern, Lawrence J.
dc.date2022-08-11T08:11:02.000
dc.date.accessioned2022-08-23T17:29:41Z
dc.date.available2022-08-23T17:29:41Z
dc.date.issued2019-08-01
dc.date.submitted2019-06-12
dc.identifier.citation<p>Becerra-Artiles A, Cruz J, Leszyk JD, Sidney J, Sette A, Shaffer SA, Stern LJ. Naturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses. Eur J Immunol. 2019 Aug;49(8):1167-1185. doi: 10.1002/eji.201948126. Epub 2019 May 2. PMID: 31020640. <a href="https://doi.org/10.1002/eji.201948126">Link to article on publisher's site</a></p>
dc.identifier.issn0014-2980 (Linking)
dc.identifier.doi10.1002/eji.201948126
dc.identifier.pmid31020640
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50374
dc.description.abstractHuman herpes virus 6B (HHV-6B) is a widespread virus that infects most people early in infancy and establishes a chronic life-long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV-6B, but antigenic targets and functional characteristics of the CD4 T-cell response are poorly understood. We identified 25 naturally processed MHC-II peptides, derived from six different HHV-6B proteins, and showed that they were recognized by CD4 T-cell responses in HLA-matched donors. The peptides were identified by mass spectrometry after elution from HLA-DR molecules isolated from HHV-6B-infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T-cell responses in vitro. T-cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3(+) CD4(+) , produced IFN-gamma, TNF-alpha, and low levels of IL-2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide-pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long-term control of HHV-6B infection.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31020640&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1002/eji.201948126
dc.subjectCD4 T cells
dc.subjectHHV-6B
dc.subjectMHC-II-eluted peptides
dc.subjectcytotoxicity
dc.subjectpolyfunctional response
dc.subjectUMCCTS funding
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCells
dc.subjectEnzymes and Coenzymes
dc.subjectImmunology and Infectious Disease
dc.subjectTranslational Medical Research
dc.subjectViruses
dc.titleNaturally processed HLA-DR3-restricted HHV-6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T-cell responses
dc.typeJournal Article
dc.source.journaltitleEuropean journal of immunology
dc.source.volume49
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/umccts_pubs/201
dc.identifier.contextkey14724587
html.description.abstract<p>Human herpes virus 6B (HHV-6B) is a widespread virus that infects most people early in infancy and establishes a chronic life-long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV-6B, but antigenic targets and functional characteristics of the CD4 T-cell response are poorly understood. We identified 25 naturally processed MHC-II peptides, derived from six different HHV-6B proteins, and showed that they were recognized by CD4 T-cell responses in HLA-matched donors. The peptides were identified by mass spectrometry after elution from HLA-DR molecules isolated from HHV-6B-infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T-cell responses in vitro. T-cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3(+) CD4(+) , produced IFN-gamma, TNF-alpha, and low levels of IL-2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide-pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long-term control of HHV-6B infection.</p>
dc.identifier.submissionpathumccts_pubs/201
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentMass Spectrometry Facility
dc.contributor.departmentDepartment of Pathology
dc.source.pages1167-1185


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