ANTIGEN RECEPTOR ENGAGEMENT DELIVERS A STOP SIGNAL TO MIGRATING T-LYMPHOCYTES

We investigated the role of the T cell antigen receptor (TcR) in contr ol of T cell migration in an in vitro system. We used T cells from tra nsgenic mice bearing a TcR for the lysozyme peptide 48-62 bound to I-A (k) (3A9). T cells from the 3A9 TcR transgenic mice crawled on purifie d intercellular adhesion molecule-1 substrates, but strikingly, stoppe d upon interaction with the physiological ligand, i.e., the mouse I-A( k) with covalently attached hen egg white lysozyme peptide residues 48 -62 complex. TcR-triggered stopping was reversible by treatment with a dhesion-strengthening phorbol esters. The microtubule organizing cente r of stopped cells was positioned adjacent to the site of stable cell anchorage. Direct conversion of lymphocyte function associated-1 to th e high-affinity conformation with antibodies also stopped T cells in a similar manner to antigen. Thus, physiological TcR engagement trigger s a stop signal through lymphocyte function associated-1. We propose t hat the stop signal is an early and essential event in T cell activati on that also will play an important role in control of T cell migratio n.