Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8347768 | Peptides | 2016 | 9 Pages |
Abstract
The TcTLE peptide (TLEEFSAKL) is a CD8+ T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein that is efficiently processed, presented and recognized by CD8+ T cells from chagasic patients. Since the immunogenic properties of wild-type epitopes may be enhanced by suitable substitutions in secondary anchor residues, we have studied the effect of introducing specific mutations at position 3, 6 and 7 of the TcTLE peptide. Mutations (E3L, S6V and A7F) were chosen on the basis of in silico predictions and in vitro assays were performed to determine the TcTLE-modified peptide binding capacity to the HLA-A*0201 molecule. In addition, the functional activity of peptide-specific CD8+ T cells in HLA-A2+ chagasic patients was also interrogated. In contrast to bioinformatics predictions, the TcTLE-modified peptide was found to have lower binding affinity and stability than the original peptide. Nevertheless, CD8+ T cells from chronic chagasic patients recognized the TcTLE-modified peptide producing TNF-α and INF-γ and expressing CD107a/b, though in less extension than the response triggered by the original peptide. Overall, although the amino acids at positions 3, 6 and 7 of TcTLE are critical for the peptide affinity, they have a limited effect on the immunogenic properties of the TcTLE epitope.
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Authors
Paola Lasso, Constanza Cárdenas, Fanny Guzmán, Fernando Rosas, MarÃa Carmen Thomas, Manuel Carlos López, John Mario González, Adriana Cuéllar, Josep Maria Campanera, F. Javier Luque, Concepción Judith Puerta,