Permissive geometry model

Ligand binding to the T-cell antigen receptor (TCR) evokes receptor triggering and subsequent T-lymphocyte activation. Although TCR signal transduction pathways have been extensively studied, a satisfactory mechanism that rationalizes how the information of ligand binding to the receptor is transmitted into the cell remains elusive. Models proposed for TCR triggering can be grouped into two main conceptual categories: receptor clustering by ligand binding and induction of conformational changes within the TCR. None of these models or their variations (see Chapter 6 for details) can satisfactorily account for the diverse experimental observations regarding TCR triggering. Clustering models are not compatible with the presence of preformed oligomeric receptors on the surface of resting cells. Models based on conformational changes induced as a direct effect of ligand binding, are not consistent with the requirement for multivalent ligand to initiate TCR signaling. In this chapter, we discuss the permissive geometry model. This model integrates receptor clustering and conformational change models, together with the existence of preformed oligomeric receptors, providing a mechanism to explain TCR signal initiation.