Antigen receptor engagement delivers a stop signal to migrating T lymphocytes

Michael L. Dustin, Shannon K. Bromley, Zhengyan Kan, Daniel A. Peterson, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3909-3913
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number8
DOIs
StatePublished - Apr 15 1997

Keywords

  • inflammation
  • integrins
  • locomotion
  • polarity
  • reconstitution

ASJC Scopus subject areas

  • General

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