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| - Synthetic Anticancer Vaccine Candidates: Rational Design of Antigenic Peptide Mimetics ThatActivate Tumor-Specific T-Cells
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| - A rational design approach was followed to develop peptidomimetic analogues of a cytotoxic T-cell epitopecapable of stimulating T-cell responses as strong as or stronger (heteroclytic) than those of parental antigenicpeptides. The work described herein focused on structural alterations of the central amino acids of themelanoma tumor-associated antigenic peptide Melan-A/MART-126-35 using nonpeptidic units. A screeningwas first realized in silico to select altered peptides potentially capable of fitting at the interface betweenthe major histocompatibilty complex (MHC) class-I HLA-A2 molecule and T-cell receptors (TCRs). Twocompounds appeared to be high-affinity ligands to the HLA-A2 molecule and stimulated several Melan-A/MART-1 specific T-cell clones. Most remarkably, one of them even managed to amplify the response ofone clone. Together, these results indicate that central TCR-contact residues of antigenic peptides can bereplaced by nonpeptidic motifs without loss of binding affinity to MHC class-I molecules and T-cell triggeringcapacity.
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