T cell receptor signal transduction: affinity, force and conformational change

T cell recognition of antigen and resulting proximal signaling are key steps in the initiation of the adaptive immune response. The T cell receptor interaction with antigen drives signal initiation in an affinity-dependent manner, but many aspects of this process remain incompletely understood, including what regions are responsible for structural changes in the TCR upon antigen binding, the importance of extracellular T cell receptor interactions with CD3, how structural changes are integrated with signaling components, and the role of force in signal transduction. Advances in structural modeling of the TCR-CD3 complex and the ability to quantify the affinity and biophysical nature of these molecular interactions have significantly furthered our understanding of the mechanism of transduction of T cell antigen recognition into intracellular signaling. This knowledge is paramount to understanding how T cell perform their critical role in adaptive immune responses, and for the development and improvement of immunotherapies.