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

CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis.
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DOI:
10.1002/eji.201040881
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发表时间:
2011-01
影响因子:
5.4
通讯作者:
Altmann, Daniel M.
Altmann, Daniel M.
中科院分区:
医学3区
文献类型:
--
作者:
Chu, Karen K.;Tippayawat, Patcharaporn;Walker, Nicola J.;Harding, Sarah V.;Atkins, Helen S.;Maillere, Bernard;Bancroft, Gregory J.;Lertmemongkolchai, Ganjana;Altmann, Daniel M.

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Burkholderia pseudomallei (Bp) 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 heterogeneity in immunity to Bp. Models show protection to be dependent on CD4+ cells and IFNγ, 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, while 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, 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 B. cenocepacia, associated with life-threatening cepacia complex in cystic fibrosis patients and B. mallei, which causes glanders. These findings suggest a role for LolC epitopes in multiepitope vaccine design for melioidosis and related diseases.
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