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

Sci Transl Med. 2015 Oct 21;7(310):310ra167. doi: 10.1126/scitranslmed.aac5477.


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 ~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-γ, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Leishmania / classification
  • Leishmania / enzymology
  • Leishmania / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
  • Receptors, Antigen, T-Cell / genetics


  • Antigens, Protozoan
  • Receptors, Antigen, T-Cell
  • Phosphoenolpyruvate Carboxykinase (ATP)