Joaquin Madrenas, Ronald L. Wange, Jennifer L. Wang, Noah Isakov, Lawrence E. Samelson, Ronald N. Germain Academic Article uri icon

abstract

  • Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating com- plexes into partially activating or even inhibitory ones. This study examined early TCR- dependent signals induced by such partial agonists or antagonists. In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of 4 chain phosphorylation and failed to activate associated ZAP-70 kinase. These results identify a specific step in theearly tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes. This finding may explain the different biological responses to TCR occupancy by these variant ligands. Both the developmentof immature thymocytes and the effector activities of ma-ture CD8'andCD4'T …

publication date

  • January 1, 1995