EMBO WORKSHOP REPORT: lymphocyte antigen receptor and coreceptor signaling Siena, Italy, November 6-10, 1999.

Abstract

On November 6–10, 1999, the EMBO workshop on ‘Lymphocyte antigen receptor and coreceptor signaling’ was held at the Certosa di Pontignano. Since the first EMBO workshop on the same theme held in 1997, exciting progress has been made towards further unraveling the molecular mechanisms of T and B cell activation. Novel signaling components have been identified, and their function characterized in cellular and animal models. Molecular adaptors that orchestrate the assembly of transducing complexes are dominating the scene for their role in signal initiation, integration, amplification and extinction. Insight has been been gained into the mechanisms regulating thresholds for receptor signaling and on the role of accessory membrane receptors in this process. Furthermore, new concepts have been brought to light, such as the requirement for antigen receptors to signal within specialized lipid microdomains and the highly ordered configuration of receptors and signaling effectors in the membrane area where T cell contacts the antigen‐presenting cell. Antigen receptor signaling has become a paradigm of signal coordination by cell surface receptors in general. Here we shall present an overview of the topics discussed at the workshop in the context of the development of the field over the last 2 years. ### Spatial and temporal orchestration of antigen receptor signaling Ordered clustering of receptors and signaling components at the immunological synapse When T cells interact with antigen‐presenting cells (APCs), the antigen receptors and associated signaling molecules colocalize in a tight area of contact between the cells, which has been termed the immunological synapse. Concomitant with activation, this area becomes a highly ordered platform that favors signal delivery (van der Merwe et al ., 2000). Receptors and intracellular proteins clustered at the contact area between T cell and APC segregate into spatially distinct domains, referred to as: (i) cSMAC (central supramolecular activation clusters), which includes the TCR, CD4, the protein tyrosine kinases (PTK) Fyn and …