A synaptic basis for T-lymphocyte activation.

T lymphocytes respond to foreign antigen by forming specialized junctions with antigen-presenting cells (APC) or target cells. A hypothesis is presented, illustrating the similarity between the T-cell recognition-activation process and the cell communication processes found in other organ systems, especially the nervous system. Based on data showing that a major neuronal protein, Thy-1, is also a mitogenic site on T cells, and based on predictions for the structures of the T-cell receptor (TcR) and Ia proteins, an activation model is presented as follows. 1) The T-cell receptor initiates cell-cell contact with the APC by interacting with Ia and antigen, forming an antigen-binding site. 2) Sets of adhesion molecules then bind, focusing the interacting proteins to the junctional site. One binding protein, L3/T4, binds Ia and concentrates the Ia molecules to the contact site. 3) The two-chain TcR then links together the TcR-Ia-antigen complexes, forming a linear chain of receptors which will self-associate once reaching a critical length, forming a cluster. This cluster juxtaposes associated channel subunits, the T3 membrane molecules, creating an ion channel, stimulating the T cell. 4) The MHC molecule is structurally a part of this activation complex, and therefore also forms a cluster on the APC surface, possibly activating the presenting cell. 5) Secretory products are then released into the synaptic site allowing for efficient and directed cell-cell communication. Cytolytic class-I-restricted cells use a similar pathway to focus the effect of cytolytic proteins. This analogy views neuronal communication and lymphoid recognition as evolutionary descendents of a primordial lymphocytic type of cell interaction.