Discovery of mechanistic basis of nascent T cell receptors Self-oligomerization by electrostatic interaction confers autonomous signaling

December 5, 2005 PRESS RELEASE

When immune cells sense extracellular signals through cell surface receptors, they transduce such signals into various biological responses via cellular signaling machinery. It is widely thought that oligomerization of receptors by binding to a specific ligand is the trigger of such signal transduction.

However, RCAI deputy director Dr. Takashi Saito and Dr. Sho Yamasaki of the Laboratory for Cell Signaling found that pre-TCR spontaneously forms oligomers through charged residues. Furthermore, alteration of these residues eliminated the ability of pre-TCR to support normal T cell development in vivo.

On the other hand, pre-TCR-mediated signaling is reported to be involved in the onset and maintenance of certain types of acute lymphoblastic leukemia. Thus, the present findings may provide a new therapeutic approach through the blockade of electrostatic oligomerization of pre-TCR by specific chemicals or antibodies.