T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis
| Autor: | Manutsanun Sumonwiriya, Kemajittra Jenjaroen, Julie A. Musson, Susanna Dunachie, Matthew T. G. Holden, Pagnarith Yos, Amelie Goudet, Kathryn J. Quigley, Ganjana Lertmemongkolchai, Julia Makinde, Daniel M. Altmann, Saskia Overbeek, Gregory J. Bancroft, John H. Robinson, Rosemary J. Boyton, Vanaporn Wuthiekanun, Bernard Maillere, Natasha Spink, Jiten Manji, Catherine B. Reynolds, Darawan Rinchai |
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| Přispěvatelé: | University of St Andrews. School of Medicine, University of St Andrews. Infection Group, University of St Andrews. Biomedical Sciences Research Complex |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Burkholderia pseudomallei
Infectious Disease and Host Response Melioidosis Genotype T cell Immunology NDAS Epitopes T-Lymphocyte Mice Transgenic Human leukocyte antigen Adaptive Immunity Epitope Microbiology Mice SDG 3 - Good Health and Well-being medicine Animals Humans Immunology and Allergy QR180 Immunology Antigens Bacterial biology Immunodominant Epitopes Histocompatibility Antigens Class II Peroxiredoxins biochemical phenomena metabolism and nutrition Acquired immune system medicine.disease biology.organism_classification medicine.anatomical_structure QR180 bacteria Intracellular |
| Zdroj: | The Journal of Immunology Author Choice |
| ISSN: | 0022-1767 |
| Popis: | 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.). 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. Publisher PDF |
| Databáze: | OpenAIRE |
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