Potent T cell agonism mediated by a very rapid TCR/pMHC interaction

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Abstract
The interaction between T cell receptors (TCR) and peptide‐major histocompatibility complex (pMHC) antigens can lead to varying degrees of agonism (T cell activation), or antagonism. The P14 TCR recognises the lymphocytic choriomeningitis virus (LCMV)‐derived peptide, gp33 residues 33–41 (KAVYNFATC), presented in the context of H‐2Db. The cellular responses to various related H‐2Db peptide ligands are very well characterised, and P14 TCR‐transgenic mice have been used extensively in models of virus infection, autoimmunity and tumour rejection. Here, we analyse the binding of the P14 soluble TCR to a broad panel of related H‐2Db‐peptide complexes by surface plasmon resonance, and compare this with their diverse cellular responses. P14 TCR binds H‐2Db‐gp33 with a KD of 3 µM (±0.5 µM), typical of an immunodominant antiviral TCR, but with unusually fast kinetics (koff = 1 s–1), corresponding to a half‐life of 0.7 s at 25°C, outside the range previously observed for murine agonist TCR/pMHC interactions. The most striking feature of these data is that a very short half‐life does not preclude the ability of a TCR/pMHC interaction to induce antiviral immunity, autoimmune disease and tumour rejection.