Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells.
Sci Transl Med
; 7(310): 310ra167, 2015 Oct 21.
Article
in En
| MEDLINE
| ID: mdl-26491077
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 ~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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD4-Positive T-Lymphocytes
/
Leishmania
/
Antigens, Protozoan
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Sci Transl Med
Journal subject:
CIENCIA
/
MEDICINA
Year:
2015
Document type:
Article
Affiliation country:
Canada