The Goldilocks model for TCR-too much attraction might not be best for vaccine design

Abstract

Recent research on T cell-antigen interactions suggests that tighter binding is not always better at eliciting an effective immune response.

Figure 1. Summary of Corse's findings and the controversy.

Corse and colleagues studied peptides that bind with increasing affinity in the TCR-peptide-MHC interaction. In vitro, T cell response increases as the affinity increases. In vivo, T cell function and expression of signaling-related molecules peaks at an intermediate affinity. The same CD4+ T cells from a transgenic mouse were used in both the in vitro and in vivo experiments. These results contrast with those from related studies using different types of T cells and experimental conditions. Specifically, Zehn and colleagues examined how stimulation of CD8+ T cells from a transgenic mouse responded to cognate peptides with increasing affinity and found a direct correlation between affinity and the number of T cells, as indicated in red. (Signaling-related molecules were not examined in this study.)