with productive immune synapses A ligand-induced conformational change in the T cell receptor associated

ABSTRACT Triggering of the T cell receptor (TCR) can produce very different responses depending on the nature of the Major Histocompatibility Complex/antigen peptide (MHCp) ligand. The molecular mechanisms that permit such fine discrimination are still unknown. We show here that an epitope in the cytoplasmic tail of the TCR CD3e subunit, recognized by antibody APA1/1, is only detected when the TCR is fully activated. Exposure of the APA1/1 epitope is shown to be fast, independent of tyrosine kinase activity and takes place even when T cells are stimulated at 0oC. These results suggest that APA1/1 detects a conformational change in the TCR. APA1/1 staining concentrates in a restricted area of the immunological synapse. Most important, we show that full agonist but not partial agonist peptides induce exposure of the APA1/1 epitope, indicating a correlation between the induction of the conformational change in the TCR and full T cell activation. Finally, the conformational change is shown to occur in T cells that are being stimulated by antigen