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dc.contributor.authorReynolds, Catherine
dc.contributor.authorGoudet, Amélie
dc.contributor.authorJenjaroen, Kemajittra
dc.contributor.authorSumonwiriya, Manutsanun
dc.contributor.authorRinchai, Darawan
dc.contributor.authorMusson, Julie
dc.contributor.authorOverbeek, Saskia
dc.contributor.authorMakinde, Julia
dc.contributor.authorQuigley, Kathryn
dc.contributor.authorManji, Jiten
dc.contributor.authorSpink, Natasha
dc.contributor.authorYos, Pagnarith
dc.contributor.authorWuthiekanun, Vanaporn
dc.contributor.authorBancroft, Gregory
dc.contributor.authorRobinson, John
dc.contributor.authorLertmemongkolchai, Ganjana
dc.contributor.authorDunachie, Susanna
dc.contributor.authorMaillere, Bernard
dc.contributor.authorHolden, Matthew
dc.contributor.authorAltmann, Daniel
dc.contributor.authorBoyton, Rosemary
dc.date.accessioned2015-05-28T16:10:06Z
dc.date.available2015-05-28T16:10:06Z
dc.date.issued2015-05-15
dc.identifier.citationReynolds , C , Goudet , A , Jenjaroen , K , Sumonwiriya , M , Rinchai , D , Musson , J , Overbeek , S , Makinde , J , Quigley , K , Manji , J , Spink , N , Yos , P , Wuthiekanun , V , Bancroft , G , Robinson , J , Lertmemongkolchai , G , Dunachie , S , Maillere , B , Holden , M , Altmann , D & Boyton , R 2015 , ' T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei : a correlate of disease outcome in acute melioidosis ' , The Journal of Immunology , vol. 194 , no. 10 , pp. 4814-4824 . https://doi.org/10.4049/jimmunol.1402862en
dc.identifier.issn0022-1767
dc.identifier.otherPURE: 188980927
dc.identifier.otherPURE UUID: 1e5d2353-829a-4132-b960-a80afeecade5
dc.identifier.otherPubMed: 25862821
dc.identifier.otherScopus: 84929119016
dc.identifier.otherORCID: /0000-0002-4958-2166/work/60196424
dc.identifier.otherWOS: 000353728800024
dc.identifier.urihttp://hdl.handle.net/10023/6708
dc.descriptionThis work was supported by National Institutes of Health–National Institute of Allergy and Infectious Diseases Large Scale T Cell Epitope Discovery Program Contract HHSN27220090046C (to R.B. and D.A.), the Welton Foundation (to R.B.), the National Institute for Health Research Biomedical Research funding scheme (to R.B. and D.A.), and a Wellcome Trust Intermediate Clinical Fellowship award (WT100174AIA; to S.D.).en
dc.description.abstractThere is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase (AhpC) of B. pseudomallei is strongly immunogenic for T cells of 'humanized' HLA transgenic mice and seropositive human donors. Some T cell epitopes, such as p6, are able to bind diverse HLA class II heterodimers and stimulate strong T cell immunity in mice and humans. Importantly, patients with acute melioidosis who survive infection show stronger T cell responses to AhpC relative to those who do not. Although the sequence of AhpC is virtually invariant among global B. pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal truncation of the p6 T cell epitope, raising the possibility of selection by host immunity. This variant peptide is virtually unable to stimulate T cell immunity. For an infection in which there has been debate about centrality of T cell immunity in defense, these observations support a role for T cell immunity to AhpC in disease protection.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofThe Journal of Immunologyen
dc.rightsCopyright © 2015 The Authors. This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/).en
dc.subjectQR180 Immunologyen
dc.subjectNDASen
dc.subject.lccQR180en
dc.titleT cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei : a correlate of disease outcome in acute melioidosisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection Groupen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.4049/jimmunol.1402862
dc.description.statusPeer revieweden


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