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

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.