Kinetic-proofreading model of TCR–pMHC binding affinity: naive T-cells scan an antigen-presenting cell's MHC-peptide complexes; only sustained high-affinity engagement (Signal 1) plus costimulation (Signal 2) primes an effector T-cell.
Kinetic proofreading: a bound TCR must survive several sequential biochemical checkpoints before it signals. Higher affinity (lower KD) lowers the TCR–pMHC off-rate, so the bond survives long enough to clear that checkpoint chain — weak/self-peptide binders usually dissociate first, which is how the immune system discriminates real threats from background noise.