T-CELL RECEPTOR-MHC CLASS-I PEPTIDE INTERACTIONS - AFFINITY, KINETICS, AND SPECIFICITY

The critical discriminatory event in the activation of T lymphocytes b earing alpha beta T cell receptors (TCRs) is their interaction with a molecular complex consisting of a peptide bound to a major histocompat ibility complex (MHC)-encoded class I or class II molecule on the surf ace of an antigen-presenting cell. The kinetics of binding were measur ed of a purified TCR to molecular complexes of a purified soluble anal og of the murine MHC class I molecule H-2L(d) (sH-2L(d)) and a synthet ic octamer peptide p2CL in a direct, real-time assay based on surface plasmon resonance. The kinetic dissociation rate of the MHC-peptide co mplex from the TCR was rapid (2.6 x 10(-2) second(-1), corresponding t o a half-time for dissociation of approximately 27 seconds), and the k inetic association rate was 2.1 x 10(5) M(-1) second(-1). The equilibr ium constant for dissociation was approximately 10(-7) M. These values indicate that TCRs must interact with a multivalent array of MHC-pept ide complexes to trigger T cell signaling.