The stoichiometry of the T cell antigen receptor and its implications for the signal transduction mechanism

Abstract

The T cell antigen receptor (TCR·CD3) is a multi-subunit complex mediating T cell development and activation. The molecular mechanism of how this receptor transmits information across the membrane is still an enigma. The stoichiometry and architecture of this receptor in the membrane are under intense investigation, since they are important in deciphering the signal transduction mechanism of the TCR·CD3. This review highlights the evidence that TCR·CD3 is found on unstimulated T cells in monovalent (one ligand-binding site per receptor) as well as in multivalent forms. Distinct detergents affect the integrity of the multivalent receptor differently, explaining controversial findings of TCR·CD3 stoichiometries as determined by biochemical means. The existence of multivalent receptors is not compatible with current models of TCR·CD3 triggering. Therefore, I discuss the novel “permissive geometry model” that combines multivalent TCR·CD3s, the requirement for multimeric ligands for receptor triggering and conformational changes at CD3.