Receptors and ligands implicated in human T cell costimulatory processes

It is well established that full activation of T cells that recognize antigens requires additional signals. These second signals are generated by the interaction of costimulatory ligands expressed on antigen presenting cells with their receptors on T cells. In addition, T cell activation processes are negatively regulated by inhibitory costimulatory pathways. Interaction of members of the B7 and the TNF superfamilies with members of the CD28 and TNF-R-superfamilies plays major roles in costimulatory processes. However, a large number of molecules that do not belong to these families have been reported to be involved in the generation of T cell costimulatory signals. In addition to well-defined costimulatory pathways, where both receptors and ligands are known, there are many T cell surface molecules that have been described to generate a second signal under certain experimental conditions, f.i. when ligated with antibodies. Furthermore there are several ligands that have been shown to positively or negatively modulate T cell activation by interacting with as of yet unknown T cell receptors. Here we give a comprehensive overview of molecules that have been implicated in human T cell activation processes and propose criteria that define genuine T cell costimulatory pathways.