Visualizing CTL activity for different CD8+ effector T cells supports the idea that lower TCR/epitope avidity may be advantageous for target cell killing

Time-lapse video microscopy allows analysis of the interaction between individual CTLs and adherent peptide-pulsed targets, from contact, to lymphocyte detachment, APC rounding, phosphatidylserine exposure and finally loss of plasma membrane integrity characteristic of end-stage apoptosis. Using in vitro-stimulated effectors specific for the ovalbumin K^bOVA₂₅₇ (OT-I) and influenza A virus D^bNP₃₆₆ and D^bPA₂₂₄ epitopes, no significant correlation was found between the duration of CTL contact and the time to phosphatidylserine exposure or loss of membrane integrity. Furthermore, there were minimal indications that transgenic T cells specific for the K^bOVA₂₅₇ epitope (TCR) diversity had any effect. However, when the analysis was repeated with D^bNP₃₆₆ and D^b PA₂₂₄-specific CTLs recovered directly from the lungs of mice with influenza pneumonia, the lower avidity D^bNP₃₆₆ -specific set was found to elute much more quickly. Shorter contact time may allow individual CTLs to lyse more targets, suggesting that lower TCR/epitope avidity may be more beneficial than higher epitope avidity for cell-mediated immunity.