ICAM-1 forms a sickle-like shape on T cells in the presence of antagonists.
Certain antigen variants, called antagonists, interfere with a T cell's ability to respond to otherwise stimulatory antigens. Although they are often effective only at high concentrations, antagonists may be used—either by pathogens or as therapies against autoimmune diseases—to thwart strong defense responses. But just how they get in the way is unclear. In the new work, the authors show ways in which antagonists hinder the formation of the immunological synapse—the junction between the T cell and the APC that contains peptide-MHC molecules, T cell receptors (TCRs), and adhesion proteins.
Synapses that formed on membranes containing excess antagonists were sparse in MHC clusters. Fewer MHCs means less T cell proliferation and cytokine production, probably because fewer TCRs are engaged. Even long after antagonist was removed, the T cells still did not respond when exposed to active antigens. In their half-active state, T cells migrated past their antigenic targets rather than making the normal full stop.
This crippling of T cell adhesion appears to result from a failure to focus adhesion rather than a failure in integrin activation itself. The ICAM-1 adhesion molecule, which is a measure of active integrins, was equally dense in synapses with or without antagonists. With antagonists, ICAM-1 accumulated in a crescent shape, not the tight circular pattern characteristic of a strong synapse. ICAM-1 is probably pushed into this odd pattern by the continued cell movement. ▪
