T Cell Signaling and Activation on Microfabricated Artificial Antigen-Presenting Cell
Friday, April 19, 2013 – ( 2:00 pm to 3:00 pm )
Location: Burchard 430, Stevens Institute of Technology
Joung-Hyun (Helen) Lee
Postdoctoral Research Fellow
Biomedical Engineering, Columbia University, New York, NY
T cells play a key role in mediating adaptive immunity. Communication between T cells and antigen-presenting cells (APCs) form an essential regulatory point of the immune system, mediated by interactions between cell-surface proteins in a small intercellular contact area termed the immunological synapse (IS). I will discuss a few examples of our efforts to emulate the interface between T cell and artificial APC by recapitulating key features of physiological synapses and precisely manipulate them using microfabrication techniques. We have demonstrated that T cell receptor (TCR) activation was promoted by spatial control of binding sites of TCR-MHC as well as CD28—CD80, which was accomplished by replacing the APC with a planar substrate containing highdensity arrays of antigenic and costimulatory signals. Further we have confirmed that the high membrane mobility of mouse T cells facilitated costimulation by CD28. Currently, we are working on effect of exclusion of CD45, a transmembrane protein tyrosine phosphatase, on activation of T cells. CD45 is known to modulate T cell signaling, but at the same time it has been argued that exclusion of CD45 from the vicinity of the TCR is necessary for activation of T cells. We fabricated surfaces by defining 1- or 2-μm diameter features of PLL-g-PEG onto coverslips, followed by adsorption of anti-CD45 to the remaining regions. These substrates depleted CD45 from the PLL-g-PEG patterned regions and enhanced production of pZap70, zeta associated protein of 70 kDa tyrosine kinase, over levels observed on uniformly coated anti-CD45 surfaces. These results demonstrate that local control over CD45 distribution can alter T cell signaling, independent of TCR–MHC recognition.
Joung-Hyun (Helen) Lee received her BS and MS degrees in Chemistry from Korea in 1997. She then worked for Samsung in developing organic electroluminescent display devices (OLED) as a researcher until she moved to the US for pursuing her Ph.D at Materials Science and Engineering in Stevens Institute of Technology in 2004. Dr. Lee conducted her doctoral research in developing microfluidic platforms to emulate microenvironments of implanttissue interface and studying complex interplay among host tissue, pathogens and drugs in physiologically relevant environment. After completing her Ph.D. in 2010, she currently works at Biomedical Engineering in Columbia University as a postdoctoral research fellow conducting research on emulating T cell-APC interactions on microfabricated biological setting. She received F32 postdoctoral fellowship award from NIH in 2012. Dr. Lee’s research interests reside on microand nano-scale fabrication thus emulation of biological systems recapitulating key features of cell-cell and cell-matrix signaling and interactions.