Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse
Figure 3
Effects of TCR/pMHC kinetics (, half-life) on T cell activation for naïve and effector T cells. TCR/pMHC interactions that are short-lived are discriminated by the TCR as nonligands in such a way to avoid the recognition of self-pMHC complexes and the activation of autoreactive T cells that may be harmful for the host (left). A model for such discrimination is termed the kinetics proofreading model. On the other hand, experimental data from our group supports a model for TCR serial engagement for T cell activation (right). That is, prolonged TCR/pMHC half-life interactions also fail to efficiently activate T cells in response to these ligands. Combining both, the kinetics proofreading model and the TCR serial engagement model, an optimal TCR/pMHC dwell time is required for efficient T cell activation (center). Optimal T cell activation at intermediate TCR/pMHC half-life interactions is supported by in vitro results using a viral peptide (naïve T cell activation) and in vivo data assessing either bacteria infection or tumor growth in mice (CTL activity).
