Revisiting T cell antigen discrimination
Biomaths (Mathematics) – EPSRC CMPH Seminar by Dr Omer Dushek (University of Oxford)

T cells are white blood cells that patrol the body for the molecular signatures (‘antigens’) of infection and cancer. When their T cell antigen receptors recognise these antigens, they can become activated to initiate immune responses that can clear these threats. Remarkably, it has been reported that the T cell receptor is exquisitely sensitive to the antigen affinity so that even a 3-fold reduction can abolish T cell activation even when increasing the antigen concentration by 100,000-fold. This unique ability of the T cell receptor has been termed perfect or absolute antigen discrimination. In this talk, I will provide a review of the original data and mathematical models formulated to understand the mechanism of antigen discrimination highlighting that previous work has focused on T cell receptor intrinsic mechanisms. I will then present our recent work showing that antigen discrimination by the T cell receptor is impaired in the absence of other, accessory, receptor/ligand interactions. By fitting models to this data, we can identify the molecular mechanisms by which these other receptors modulate kinetic proofreading. The role of these other interactions in cancer immune therapy will be discussed.