CSB Seminar: Dr. John Hammer, Molecular Cell Biology Section, National Institutes of Health

CSB Departmental Seminar

Dr. John Hammer
Molecular Cell Biology Section
National Institutes of Health
Bethesda, MD

“Revealing the Secrets of T Cell Immunological Synapse Formation and Function using Super Resolution Imaging”

Host: Prof. Sergey Plotnikov

Refreshments will be served. All are welcome!

Video Conferencing at UTM (HSC 332) & UTSc (MW 229)

Abstract:
Upon antigen recognition, actin assembly and inward flow in the plane of the radially symmetric immunological synapse (IS) drives the centralization of T cell receptor microclusters (TCR MCs) and the integrin LFA-1. Using two forms of structured-illumination microscopy (SIM), we have found that actin arcs populating the medial, lamella-like region of the IS arise from linear actin filaments generated by one or more formins present at the distal edge of the IS. After traversing the outer, Arp2/3-generated, lamellopodia-like region of the IS, these linear filaments are organized by myosin II into concentric arcs that should possess the anti-parallel organization required for contraction. Quantitative, fixed-cell 3D-SIM shows that open, active LFA-1 often aligns with arcs while TCR MCs commonly reside between arcs, and live-cell TIRF-SIM shows TCR MCs being swept inward by arcs. Consistently, disrupting actin arc formation via formin inhibition results in less centralized TCR MCs, miss-segregated integrin clusters, decreased T: B cell adhesion frequency, and diminished proximal TCR signaling. Together, our results define the origin, organization, and functional significance of a major actomyosin contractile structure at the IS that directly propels TCR MC transport.