Antigen receptor engagement delivers a stop signal to migrating T lymphocytes

Antigen receptor engagement delivers a stop signal to migrating T lymphocytes

Center for Immunology and Department of Pathology, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110

Abstract

We investigated the role of the T cell antigen receptor (TcR) in control of T cell migration in an in vitro system. We used T cells from transgenic 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 purified intercellular adhesion molecule-1 substrates, but strikingly, stopped 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 adhesion-strengthening phorbol esters. The microtubule organizing center of stopped cells was positioned adjacent to the site of stable cell anchorage. Direct conversion of lymphocyte function associated-1 to the high-affinity conformation with antibodies also stopped T cells in a similar manner to antigen. Thus, physiological TcR engagement triggers a stop signal through lymphocyte function associated-1. We propose that the stop signal is an early and essential event in T cell activation that also will play an important role in control of T cell migration.

locomotion/inflammation/reconstitution/polarity/integrins

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: dustin{at}pathbox.wustl.edu.
Emil R. Unanue
ABBREVIATIONS:

APC,

antigen-presenting cell;

HEL,

hen egg white lysozyme;

I-Ak–HEL48–62,

mouse I-Ak with covalently attached hen egg white lysozyme peptide residues 48–62;

ICAM-1,

intercellular adhesion molecule-1;

LFA-1,

lymphocyte function associated-1;

MHC,

major histocompatibility complex;

MTOC,

microtubule organizing center;

PMA,

phorbol 12-myristate 13-acetate;

TcR,

T cell antigen receptor