Cutting edge: LFA-1 integrin-dependent T cell adhesion is regulated by both ag specificity and sensitivity.
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.
Mueller
Kristen L
KL
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Daniels
Mark A
MA
Felthauser
Alicia
A
Kao
Charlly
C
Jameson
Stephen C
SC
Shimizu
Yoji
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019061:src-Family Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases