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dc.contributor.authorOlvera-Gomez, Irlanda
dc.contributor.authorHamilton, Sara E.
dc.contributor.authorXiao, Zhengguo
dc.contributor.authorGuimaraes, Carla P.
dc.contributor.authorPloegh, Hidde
dc.contributor.authorHogquist, Kristin A.
dc.contributor.authorWang, Liangchun
dc.contributor.authorJameson, Stephen C.
dc.date.accessioned2012-09-05T15:47:29Z
dc.date.available2012-09-05T15:47:29Z
dc.date.issued2012-01
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/72523
dc.description.abstractThe ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT–antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option.en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1105771109en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleCholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccinationen_US
dc.typeArticleen_US
dc.identifier.citationOlvera-Gomez, I. et al. “Cholera Toxin Activates Nonconventional Adjuvant Pathways That Induce Protective CD8 T-cell Responses After Epicutaneous Vaccination.” Proceedings of the National Academy of Sciences 109.6 (2012): 2072–2077. Copyright ©2012 by the National Academy of Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.approverPloegh, Hidde
dc.contributor.mitauthorPloegh, Hidde
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsOlvera-Gomez, I.; Hamilton, S. E.; Xiao, Z.; Guimaraes, C. P.; Ploegh, H. L.; Hogquist, K. A.; Wang, L.; Jameson, S. C.en
dc.identifier.orcidhttps://orcid.org/0000-0002-1090-6071
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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