Imperial College London
Portrait Picture

ProfessorDannyAltmann

Faculty of Medicine, Department of Immunology and Inflammation

Professor of Immunology
 
 
 
//

Contact

 

+44 (0)20 3313 8212d.altmann

 
 
//

Location

 

5S5CHammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Nithichanon:2018:10.3389/fimmu.2018.00484,
author = {Nithichanon, A and Rinchai, D and Buddhisa, S and Saenmuang, P and Kewcharoenwong, C and Kessler, B and Khaenam, P and Chetchotisakd, P and Maillere, B and Robinson, J and Reynolds, CJ and Boyton, RJ and Altmann, DM and Lertmemongkolchai, G},
doi = {10.3389/fimmu.2018.00484},
journal = {Frontiers in Immunology},
title = {Immune control of Burkholderia pseudomallei––common, high-frequency T-cell responses to a broad repertoire of immunoprevalent epitopes},
url = {http://dx.doi.org/10.3389/fimmu.2018.00484},
volume = {9},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Burkholderia pseudomallei (Bp) is an environmental bacterial pathogen that causes potentially lethal sepsis in susceptible individuals and is considered a Category B, Tier-1 biothreat agent. As such, it is crucial to gain an improved understanding of protective immunity and potential vaccine candidates. The nature of immune correlates dictating why most exposed individuals in endemic regions undergo asymptomatic seroconversion while others succumb to life-threatening sepsis is largely uncharted. Bp seroreactive, immunogenic proteins have previously been identified by antigen microarray. We here set out to conduct an analysis of T-cell recognition of the Bp immunome using serodominant antigens represented in the original antigen microarray, examining immune correlates of disease in healthy seropositive individuals and those with acute disease or in convalescence. By screening a library of 739 overlapping peptides representing the sequences of 20 different Bp antigens, we aimed to define immune correlates of protection at the level of immunoprevalent T-cell epitopes. Responses to a large number of epitopes were common in healthy seropositive individuals: we found remarkably broad responsiveness to Bp epitopes, with 235 of 739 peptides recognized by ≥80% of all tested donors. The cumulative response to Bp epitopes in healthy, seropositive, donors from this endemic region were of the order of thousands of spot forming cells per million cells, making Bp recognition a significant component of the T-cell repertoire. Noteworthy among our findings, analysis revealed 10 highly immunoprevalent T-cell epitopes, able to induce Bp-specific IFNγ responses that were high in responding T-cell frequency within the repertoire, and also common across individuals with different human leukocyte antigen types. Acute melioidosis patients showed poor T-cell responses to the immunoprevalent epitopes, but acquired responsiveness following recovery from infection. Our findings suggest
AU  - Nithichanon,A
AU  - Rinchai,D
AU  - Buddhisa,S
AU  - Saenmuang,P
AU  - Kewcharoenwong,C
AU  - Kessler,B
AU  - Khaenam,P
AU  - Chetchotisakd,P
AU  - Maillere,B
AU  - Robinson,J
AU  - Reynolds,CJ
AU  - Boyton,RJ
AU  - Altmann,DM
AU  - Lertmemongkolchai,G
DO  - 10.3389/fimmu.2018.00484
PY  - 2018///
SN  - 1664-3224
TI  - Immune control of Burkholderia pseudomallei––common, high-frequency T-cell responses to a broad repertoire of immunoprevalent epitopes
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2018.00484
UR  - http://hdl.handle.net/10044/1/57490
VL  - 9
ER  -
Download