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T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei: a correlate of disease outcome in acute melioidosis

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T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei : a correlate of disease outcome in acute melioidosis. / Reynolds, Catherine; Goudet, Amélie; Jenjaroen, Kemajittra; Sumonwiriya, Manutsanun; Rinchai, Darawan; Musson, Julie; Overbeek, Saskia; Makinde, Julia; Quigley, Kathryn; Manji, Jiten; Spink, Natasha; Yos, Pagnarith; Wuthiekanun, Vanaporn; Bancroft, Gregory; Robinson, John; Lertmemongkolchai, Ganjana; Dunachie, Susanna; Maillere, Bernard; Holden, Matthew; Altmann, Daniel; Boyton, Rosemary.

In: The Journal of Immunology, Vol. 194, No. 10, 15.05.2015, p. 4814-4824.

Research output: Contribution to journalArticle

Harvard

Reynolds, 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.1402862

APA

Reynolds, C., Goudet, A., Jenjaroen, K., Sumonwiriya, M., Rinchai, D., Musson, J., ... 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, 194(10), 4814-4824. https://doi.org/10.4049/jimmunol.1402862

Vancouver

Reynolds C, Goudet A, Jenjaroen K, Sumonwiriya M, Rinchai D, Musson J et al. T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei: a correlate of disease outcome in acute melioidosis. The Journal of Immunology. 2015 May 15;194(10):4814-4824. https://doi.org/10.4049/jimmunol.1402862

Author

Reynolds, Catherine ; Goudet, Amélie ; Jenjaroen, Kemajittra ; Sumonwiriya, Manutsanun ; Rinchai, Darawan ; Musson, Julie ; Overbeek, Saskia ; Makinde, Julia ; Quigley, Kathryn ; Manji, Jiten ; Spink, Natasha ; Yos, Pagnarith ; Wuthiekanun, Vanaporn ; Bancroft, Gregory ; Robinson, John ; Lertmemongkolchai, Ganjana ; Dunachie, Susanna ; Maillere, Bernard ; Holden, Matthew ; Altmann, Daniel ; Boyton, Rosemary. / T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei : a correlate of disease outcome in acute melioidosis. In: The Journal of Immunology. 2015 ; Vol. 194, No. 10. pp. 4814-4824.

Bibtex - Download

@article{1e5d2353829a4132b960a80afeecade5,
title = "T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei: a correlate of disease outcome in acute melioidosis",
abstract = "There 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.",
author = "Catherine Reynolds and Am{\'e}lie Goudet and Kemajittra Jenjaroen and Manutsanun Sumonwiriya and Darawan Rinchai and Julie Musson and Saskia Overbeek and Julia Makinde and Kathryn Quigley and Jiten Manji and Natasha Spink and Pagnarith Yos and Vanaporn Wuthiekanun and Gregory Bancroft and John Robinson and Ganjana Lertmemongkolchai and Susanna Dunachie and Bernard Maillere and Matthew Holden and Daniel Altmann and Rosemary Boyton",
note = "This 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.).",
year = "2015",
month = "5",
day = "15",
doi = "10.4049/jimmunol.1402862",
language = "English",
volume = "194",
pages = "4814--4824",
journal = "The Journal of Immunology",
issn = "0022-1767",
publisher = "AMER ASSOC IMMUNOLOGISTS",
number = "10",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - T cell immunity to the alkyl hydroperoxide reductase of Burkholderia pseudomallei

T2 - a correlate of disease outcome in acute melioidosis

AU - Reynolds, Catherine

AU - Goudet, Amélie

AU - Jenjaroen, Kemajittra

AU - Sumonwiriya, Manutsanun

AU - Rinchai, Darawan

AU - Musson, Julie

AU - Overbeek, Saskia

AU - Makinde, Julia

AU - Quigley, Kathryn

AU - Manji, Jiten

AU - Spink, Natasha

AU - Yos, Pagnarith

AU - Wuthiekanun, Vanaporn

AU - Bancroft, Gregory

AU - Robinson, John

AU - Lertmemongkolchai, Ganjana

AU - Dunachie, Susanna

AU - Maillere, Bernard

AU - Holden, Matthew

AU - Altmann, Daniel

AU - Boyton, Rosemary

N1 - This 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.).

PY - 2015/5/15

Y1 - 2015/5/15

N2 - There 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.

AB - There 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.

U2 - 10.4049/jimmunol.1402862

DO - 10.4049/jimmunol.1402862

M3 - Article

VL - 194

SP - 4814

EP - 4824

JO - The Journal of Immunology

JF - The Journal of Immunology

SN - 0022-1767

IS - 10

ER -

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