T cell receptor binding kinetics required for T cell activation depend on the density of cognate ligand on the antigen-presenting cell.

摘要: CD8+ T cells recognize peptides of eight to nine amino acid residues long in the context MHC class I molecules on surface antigen-presenting (APCs). This recognition event is highly sensitive, as evidenced by fact that can be activated cognate peptide/MHC complex (pMHC) at extremely low densities (1-50 molecules). High sensitivity particularly valuable for detection antigens density, such those derived from tumor and intracellular pathogens, which down-modulate pMHCs APCs evade adaptive immune system. cell activation only triggered response interactions between receptor (TCR) pMHC ligand reach a specific half-life threshold. However, with excessively half-lives result impaired activation. Thus, efficient requires an optimal dwell time TCR-pMHC interaction. Here, we show that, although this requirement density APC surface, high epitope there no impairment extended times. observation was predicted mathematical simulations different supported experiments performed selected varied expression pMHC. According these results, effective depends interplay inherent binding kinetics APC.