查看文章

Although several cancer immunotherapy strategies are based on the use of analog peptides and on the modulation of the TCR affinity of adoptively transferred T cells, it remains unclear whether tumor-specific T cell activation by strong and weak TCR stimuli evoke different Ca 2+ signatures from the Ca 2+ intracellular stores and whether the amplitude of Ca 2+ release from the endoplasmic reticulum (ER) can be further modulated by coreceptor binding to peptide/MHC. In this study, we combined functional, structural, and kinetic measurements to correlate the intensity of Ca 2+ signals triggered by the stimulation of the 1G4 T cell clone specific to the tumor epitope NY-ESO-1 157–165. Two analogs of the NY-ESO-1 157–165 peptide, having similar affinity to HLA-A2 molecules, but a 6-fold difference in binding affinity for the 1G4 TCR, resulted in different Ca 2+ signals and T cell activation. 1G4 stimulation by the …