CD4(+) T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis.


Chu, KK; Tippayawat, P; Walker, NJ; Harding, SV; Atkins, HS; Maillere, B; Bancroft, GJ; Lertmemongkolchai, G; Altmann, DM; (2011) CD4(+) T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis. European journal of immunology, 41 (1). pp. 107-15. ISSN 0014-2980 DOI: https://doi.org/10.1002/eji.201040881

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Abstract

Burkholderia pseudomallei causes melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. This spectrum of host-pathogen interactions poses challenging questions about the heterogeneity in immunity to B. pseudomallei. Models show protection to be dependent on CD4(+) cells and IFN-?, but little is known about specific target antigens. Having previously implicated the ABC transporter, LolC, in protective immunity, we here use epitope prediction, HLA-binding studies, HLA-transgenic models and studies of T cells from seropositive individuals to characterize HLA-restricted LolC responses. Immunized mice showed long-lasting memory to the protein, whereas predictive algorithms identified epitopes within LolC that subsequently demonstrated strong HLA class II binding. Immunization of HLA-DR transgenics with LolC stimulated T-cell responses to four of these epitopes. Furthermore, the responsiveness of HLA transgenics to LolC revealed a hierarchy supportive of HLA polymorphism-determined differential susceptibility. Seropositive human donors of diverse HLA class II types showed T-cell responses to LolC epitopes, which are conserved among Burkholderia species including Burkholderia cenocepacia, associated with life-threatening cepacia complex in cystic fibrosis patients and Burkholderia mallei, which causes glanders. These findings suggest a role for LolC epitopes in multiepitope vaccine design for melioidosis and related diseases.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 21182082
Web of Science ID: 285933000012
URI: http://researchonline.lshtm.ac.uk/id/eprint/1855

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