19. September 2023 17:00 Uhr / Wissenschaftler

CMMS Seminar: TCR-pMHC complex formation triggers CD3 dynamics

von Floris van Eerden (Department of Systems Immunology, Osaka University)

CMMS Talks Teaser

Veranstaltungsort: Seminarraum 0.101

Das spezielle CMMS-Seminar begrüßt Floris van Eerden von der Abteilung für Systemimmunologie der Universität Osaka in Frankfurt.

Das Seminar wird in englischer Sprache gehalten. Daher ist auch die folgende Vortragsankündigung auf Englisch

Abstract: The T cell receptor (TCR) plays an important role in the immune system by recognizing peptide antigens presented by the major histocompatibility complex (MHC). Despite decades of research, the TCR remains enigmatic, as it is not clear how binding of an immunogenic peptide-MHC complex (pMHC) is signaled over the plasma membrane. The TCR lacks a cytoplasmic domain, but forms a complex with the CD3 proteins, which have long cytoplasmic tails that contain the ITAM motifs, which are phosphorylated upon TCR-pMHC binding. It has been conceptually difficult to understand how extracellular TCR-pMHC binding results in the phosphorylation of the ITAMs inside the cell; the TCR lacks a proper cytoplasmic domain, while the CD3 proteins are too short to interact with the pMHC. The fact that the TCR and CD3 associate non-covalently further complicates the problem. Based upon extensive molecular dynamics simulations, we present an allosteric mechanism for TCR triggering upon pMHC binding for which we obtained experimental support. van Eerden, F. J., Sherif, A. A., Llamas-Covarrubias, M. A., Millius A., Lu X., Ishizuka S., Yamasaki S., Standley D. M. (2023), TCR-pMHC complex formation triggers CD3 dynamics, eLife 12:RP88065