Visualizing the dynamics of T cell activation: intracellular adhesion molecule 1 migrates rapidly to the T cell/B cell interface and acts to sustain calcium levels.
T cell recognition typically involves both the engagement of a specific T cell receptor with a peptide/major histocompatibility complex (MHC) and a number of accessory interactions. One of the most important interactions is between the integrin lymphocyte function-associated antigen 1 (LFA-1) on the T cell and intracellular adhesion molecule 1 (ICAM-1) on an antigen-presenting cell. By using fluorescence video microscopy and an ICAM-1 fused to a green fluorescent protein, we find that the elevation of intracellular calcium in the T cell that is characteristic of activation is followed almost immediately by the rapid accumulation of ICAM-1 on a B cell at a tight interface between the two cells. This increased density of ICAM-1 correlates with the sustained elevation of intracellular calcium in the T cell, known to be critical for activation. The use of peptide/MHC complexes and ICAM-1 on a supported lipid bilayer to stimulate T cells also indicates a major role for ICAM-1/LFA-1 in T cell activation but, surprisingly, not for adhesion, as even in the absence of ICAM-1 the morphological changes and adhesive characteristics of an activated T cell are seen in this system. We suggest that T cell antigen receptor-mediated recognition of a very small number of MHC/peptide complexes could trigger LFA-1/ICAM-1 clustering and avidity regulation, thus amplifying and stabilizing the production of second messengers.
Wülfing
C
C
Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sjaastad
M D
MD
Davis
M M
MM
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002118:Calcium / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D017136:Ion Transport / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D018715:Microscopy, Video; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018799:Intercellular Adhesion Molecule-1; D002118:Calcium