ZETA-PHOSPHORYLATION WITHOUT ZAP-70 ACTIVATION-INDUCED BY TCR ANTAGONISTS OR PARTIAL AGONISTS

Small changes in the peptide-major histocompatibility complex (MHC) mo lecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or ev en inhibitory ones, This study examined early TCR-dependent signals in duced by such partial agonists or antagonists, In contrast to typical agonist ligands, both an antagonist and several partial agonists stimu lated a distinct pattern of zeta chain phosphorylation and failed to a ctivate associated ZAP-70 kinase, These results identify a specific st ep in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes, This fin ding may explain the different biological responses to TCR occupancy b y these variant ligands.