Seminar: Mike Dustin

Visualizing the syntax of immune cell communication

Date:
16 November 2016 14:30 hrs. - 15:30 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
Visualizing the syntax of immune cell communication
Speaker(s):

Mike Dustin, Kennedy Institute, University of Oxford, UK

Host(s):

Carl Figdor, Dept. of Tumor Immunology, RIMLS

16-11-2016 14:30:0016-11-2016 15:30:00Europe/AmsterdamVisualizing the syntax of immune cell communication Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Flyer


undefinedT cell activation and effector functions involve an immunological synapse.  The immunological synapse emerges from the interactions of thousands of surface receptors that move within the apposing cells membranes controlled by forces of self assembly and active cytoskeletal forces.  The emergent organization of adhesion molecules driven by antigen receptor signals provide a structure for immune cell communication.

In this context we can think of the molecules as words in a language and the immunological synapse as providing the syntax for combining the words into actionable instructions.  We will focus on the role of the integrin LFA-1 in forming an adhesion ring that excludes antigen receptor microclusters and the immunoglobulin superfamily receptor CD2 that initially co-localizes with the TCR in micro clusters, but then blossoms into a peripheral corolla that profoundly enhances Calcium ion signals and resists inhibition by checkpoint receptors. The role of this syntax in resistance to PD-1 mediated T cell exhaustion and paralysis will be discussed.

Key Publications

  • A novel adapter protein orchestrates receptor patterning and cytoskeletal polarity in T cell contacts. Cell; 94:667-77, 1998
  • T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase Ctheta. J Immunol; 181:4852-63, 2008.\
  • Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature; 507(7490):118-23, 2014

 

 



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