The kinetic-segregation model of T-cell receptor triggering Professor Simon Davis (University of Oxford) presents his work on the kinetic-segregation model of T-cell receptor triggering. Hosted by Professor Gavin Wright.

Seminar
This event has now finished.
  • Date and time: Friday 17 November 2023, 1pm to 2pm
  • Location: Dianna Bowles Lecture Theatre, B/K/018, Biology Building, Campus West, University of York (Map)
  • Audience: Open to alumni, staff, students (postgraduate researchers, taught postgraduates, undergraduates)
  • Admission: Free admission, booking not required

Event details

Abstract

The T-cell receptor (TCR) has no intrinsic enzymatic activity and is instead phosphorylated by the Src tyrosine kinase, Lck. There are three main explanations for how this occurs, including the kinetic-segregation (KS) model. The KS model postulates that the state of TCR phosphorylation is maintained by an equilibrium between kinases and phosphatases, which is disturbed locally in favour of kinases when TCRs engage their ligands, owing to the exclusion of large receptor-type tyrosine phosphatases such as CD45 from regions of cell-cell contact. I will show how the KS model accounts for, and links antigen discrimination and microvillus use by T cells, and present other evidence supporting a formal “dwell-time” treatment of the KS model and ligand-induced signaling. I will also discuss how our recent cryo-EM structure of the complex of the TCR and pMHC supports the model. Finally, I will suggest an explanation for how signaling by immune receptors is induced by superagonistic antibodies and how this could be harnessed clinically to dampen immune responses, through the activation of inhibitory receptors.

About the speaker

Professor Simon Davis

Simon is a Professor of Molecular Immunology in the Medical Sciences Division of the University of Oxford. In 1995 he established his own laboratory in what is now the Radcliffe Department of Medicine, and is now based at the MRC Weatherall Institute of Molecular Medicine, which is led by Professor KJ Patel. Simon is also a member of the MRC Human Immunology Unit, directed by Alison Simmons. His labs focus has been on the cell biology of the T-cell surface. They have developed general methods for crystalizing glycoproteins and determined the structures of key T-cell surface proteins including the first adhesion protein (CD2) and its ligand CD58, the costimulatory receptor CD28 and its ligand CD80, and the large tyrosine phosphatase CD45. The Davis Lab have also worked out how weak, specific recognition is achieved by these types of proteins and obtained the first insights into the likely overall composition of the T-cell surface. Most importantly they proposed, with PA van der Merwe, one of the most complete and best-supported explanations for leukocyte receptor triggering, called the kinetic-segregation model.