Cutting edge: LFA-1 integrin-dependent T cell adhesion is regulated by both Ag specificity and sensitivity

Kristen L. Mueller, Mark A. Daniels, Alicia Felthauser, Charlly Kao, Stephen C Jameson, Yoji Shimizu

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Ab stimulation of the TCR rapidly enhances the functional activity of the LFA-1 integrin. Although TCR-mediated changes in LFA-1 activity are thought to promote T cell-APC interactions, the Ag specificity and sensitivity of TCR-mediated triggering of LFA-1 is not clear. We demonstrate that peptide/MHC (pMHC) tetramers rapidly enhance LFA-1-dependent adhesion of OT-I TCR transgenic CD8+ T cells to purified ICAM-1. Inhibition of src family tyrosine kinase or PI3K activity blocked pMHC tetramer- and anti-CD3-stimulated adhesion. These effects are highly specific because partial agonist and antagonist pMHC tetramers are unable to stimulate OT-I T cell adhesion to ICAM-1 The Ag thresholds required for T cell adhesion to ICAM-1 resemble those of early T cell activation events, because optimal LFA-1 activation occurs at tetramer concentrations that fail to induce maximal T cell proliferation. Thus, TCR signaling to LFA-1 is highly Ag specific and sensitive to low concentrations of Ag.

Original languageEnglish (US)
Pages (from-to)2222-2226
Number of pages5
JournalJournal of Immunology
Volume173
Issue number4
DOIs
StatePublished - Aug 15 2004

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