Live-cell dynamics and the role of costimulation in immunological synapse formation

Scott A. Wetzel, Timothy W. McKeithan, David C. Parker

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Using transfected fibroblasts expressing both wild-type I-Eκ and green fluorescent protein-tagged I-Eκ with covalently attached antigenic peptide, we have monitored movement of specific MHC:peptide complexes during CD4+ T cell-APC interactions by live-cell video microscopy. Ag recognition occurs within 30 s of T cell-APC contact, as shown by a sharp increase in cytoplasmic calcium ion concentration. Within 1 min, small MHC:peptide clusters form in the contact zone that coalesce into an immunological synapse over 3-20 min. When T cells conjugated to APC move across the APC surface, they appear to drag the synapse with them. This system was used to examine the role of costimulation in the formation of the immunological synapse. Blocking CD80/CD28 or ICAM-1/LFA-1 interactions alters synapse morphology and reduces the area and density of accumulated complexes. These reductions correlate with reduced T cell proliferation, while CD69 and CD25 expression and TCR down-modulation remain unaffected. Thus, costimulation is essential for normal mature immunological synapse formation.

Original languageEnglish (US)
Pages (from-to)6092-6101
Number of pages10
JournalJournal of Immunology
Volume169
Issue number11
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Live-cell dynamics and the role of costimulation in immunological synapse formation'. Together they form a unique fingerprint.

Cite this