In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response. - Archive ouverte HAL Access content directly
Journal Articles PLoS Neglected Tropical Diseases Year : 2011

In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response.

(1) , (1) , (1) , (1) , (1) , (1) , (2) , (1) , (1) , (1) , (3) , (1)
1
2
3

Abstract

Background: As a potent CD8+ T cell activator, peptide vaccine has found its way in vaccine development against intracellular infections and cancer, but not against leishmaniasis. The first step toward a peptide vaccine is epitope mapping of different proteins according to the most frequent HLA types in a population. Methods and Findings: Six Leishmania (L.) major-related candidate antigens (CPB,CPC,LmsTI-1,TSA,LeIF and LPG-3) were screened for potential CD8+ T cell activating 9-mer epitopes presented by HLA-A*0201 (the most frequent HLA-A allele). Online software including SYFPEITHI, BIMAS, EpiJen, Rankpep, nHLApred, NetCTL and Multipred were used. Peptides were selected only if predicted by almost all programs, according to their predictive scores. Pan-A2 presentation of selected peptides was confirmed by NetMHCPan1.1. Selected peptides were pooled in four peptide groups and the immunogenicity was evaluated by in vitro stimulation and intracellular cytokine assay of PBMCs from HLA-A2+ individuals recovered from L. major. HLA-A22 individuals recovered from L. major and HLA-A2+ healthy donors were included as control groups. Individual response of HLA-A2+ recovered volunteers as percent of CD8+/IFN-c+ T cells after in vitro stimulation against peptide pools II and IV was notably higher than that of HLA-A22 recovered individuals. Based on cutoff scores calculated from the response of HLA-A22 recovered individuals, 31.6% and 13.3% of HLA-A2+ recovered persons responded above cutoff in pools II and IV, respectively. ELISpot and ELISA results confirmed flow cytometry analysis. The response of HLA-A22 recovered individuals against peptide pools I and III was detected similar and even higher than HLA-A2+ recovered individuals. Conclusion: Using in silico prediction we demonstrated specific response to LmsTI-1 (pool II) and LPG-3- (pool IV) related peptides specifically presented in HLA-A*0201 context. This is among the very few reports mapping L. major epitopes for human HLA types. Studies like this will speed up polytope vaccine idea towards leishmaniasis.
Fichier principal
Vignette du fichier
journal.pntd.0001295_2_.pdf (427.88 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

pasteur-00787351 , version 1 (05-03-2013)

Identifiers

Cite

Negar Seyed, Farnaz Zahedifard, Shima Safaiyan, Elham Gholami, Fatemeh Doustdari, et al.. In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response.. PLoS Neglected Tropical Diseases, 2011, 5 (9), pp.e1295. ⟨10.1371/journal.pntd.0001295⟩. ⟨pasteur-00787351⟩

Collections

RIIP RIIP_IRAN
135 View
508 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More