PlumX Metrics
Embed PlumX Metrics

Effect of secondary anchor amino acid substitutions on the immunogenic properties of an HLA-A*0201-restricted T cell epitope derived from the Trypanosoma cruzi KMP-11 protein

Peptides, ISSN: 0196-9781, Vol: 78, Page: 68-76
2016
  • 7
    Citations
  • 0
    Usage
  • 34
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

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.

Bibliographic Details

Lasso, Paola; Cárdenas, Constanza; Guzmán, Fanny; Rosas, Fernando; Thomas, María Carmen; López, Manuel Carlos; González, John Mario; Cuéllar, Adriana; Campanera, Josep Maria; Luque, F Javier; Puerta, Concepción Judith

Elsevier BV

Biochemistry, Genetics and Molecular Biology; Neuroscience

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know