CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis.
Chu, Karen K;
Tippayawat, Patcharaporn;
Walker, Nicola J;
Harding, Sarah V;
Atkins, Helen S;
Maillere, Bernard;
Bancroft, Gregory J;
Lertmemongkolchai, Ganjana;
Altmann, Daniel M;
(2011)
CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis.
European journal of immunology, 41 (1).
pp. 107-115.
ISSN 0014-2980
DOI: https://doi.org/10.1002/eji.201040881
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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-γ, 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.