Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells

Abstract : There is currently no clinically effective vaccine against leishmaniasis because of poor understanding of the antigens that elicit dominant T cell immunity. Using proteomics and cellular immunology, we identified a dominant naturally processed peptide (PEPCK335-351) derived from Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK). PEPCK was conserved in all pathogenic Leishmania, expressed in glycosomes of promastigotes and amastigotes, and elicited strong CD4(+) T cell responses in infected mice and humans. I-A(b)-PEPCK335-351 tetramer identified protective Leishmania-specific CD4(+) T cells at a clonal level, which comprised similar to 20% of all Leishmania-reactive CD4(+) T cells at the peak of infection. PEPCK335-351-specific CD4(+) T cells were oligoclonal in their T cell receptor usage, produced polyfunctional cytokines (interleukin-2, interferon-gamma and tumor necrosis factor), and underwent expansion, effector activities, contraction, and stable maintenance after lesion resolution. Vaccination with PEPCK peptide, DNA expressing full-length PEPCK, or rPEPCK induced strong durable cross-species protection in both resistant and susceptible mice. The effectiveness and durability of protection in vaccinated mice support the development of a broadly cross-species protective vaccine against different forms of leishmaniasis by targeting PEPCK.
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Submitted on : Friday, June 2, 2017 - 10:48:57 AM
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Z. Mou, J. Li, T. Boussoffara, H. Kishi, H. Hamana, et al.. Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells. Science Translational Medicine, American Association for the Advancement of Science, 2015, 7 (310), pp.310ra167 - 310ra167. ⟨10.1126/scitranslmed.aac5477⟩. ⟨pasteur-01375023⟩

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