Inhibitory receptor signaling destabilizes immunological synapse formation in primary NK cells.

摘要: Upon engagement of their cognate class I major histocompatibility complex (MHC) ligands, receptors containing immunotyrosine-based inhibitory motifs (ITIMs) transduce signals that block cytolytic and inflammatory responses. In this manner, ITIM-coupled play a crucial role in maintaining natural killer (NK) cell tolerance toward normal, healthy tissue. A number studies, mostly using immortalized NK lines, have demonstrated ITIM signaling functions by disrupting the immunological synapse formed between an its target. However, more recent imaging experiments primary cells suggested receptor does not antagonize contact formation, casting doubt on hypothesis destabilize synapse. To resolve issue, we analyzed activation formation supported lipid bilayers controlled combinations activating ligands. Under these conditions, observed clearly inhibited adhesion, arrest, calcium influx, three hallmarks formation. These results are consistent with previous reports showing deliver “reverse stop” signal, confirm at least part destabilizing