A Single Peptide-MHC Triggers Digital Cytokine Secretion in CD4+ T Cells

Event details
Date | 01.04.2014 |
Hour | 14:30 |
Speaker | Jun Huang, Ph.D., Stanford University, Stanford, CA (USA) |
Location | |
Category | Conferences - Seminars |
BIOENGINEERING SEMINAR
Abstract:
We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4+ T cell functional sensitivity. We found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single pMHC to secrete tumor necrosis factor alpha (TNF-a) and interleukin-2 (IL-2) cytokines with a rate of ~1,000, ~10,000, and ~10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. We also found that a single pMHC localized to the immunological synapse induced the slow formation of a long-lasting T cell receptor (TCR) cluster, consistent with a serial engagement mechanism. These data show that scaling up CD4+ T cell cytokine responses involves increasingly efficient T cell recruitment rather than greater cytokine production per cell.
Bio:
2008 Ph.D., Bioengineering, Georgia Institute of Technology, Atlanta, GA, USA (advisor: Professor Cheng Zhu)
2007 M.S., Chemical Engineering, Georgia Institute of Technology, Atlanta, GA (USA)
2003 M.S., Biomedical Engineering, Institute of Mechanics, Chinese Academy of Sciences and Chongqing University (Joint Program), Beijing, China
2000 B.S. (with honor), Chemical Engineering, Chongqing University, Chongqing, China
Postdoctoral training:
2009– Department of Microbiology and Immunology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA (advisor: Professor Mark M. Davis)
Abstract:
We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4+ T cell functional sensitivity. We found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single pMHC to secrete tumor necrosis factor alpha (TNF-a) and interleukin-2 (IL-2) cytokines with a rate of ~1,000, ~10,000, and ~10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. We also found that a single pMHC localized to the immunological synapse induced the slow formation of a long-lasting T cell receptor (TCR) cluster, consistent with a serial engagement mechanism. These data show that scaling up CD4+ T cell cytokine responses involves increasingly efficient T cell recruitment rather than greater cytokine production per cell.
Bio:
2008 Ph.D., Bioengineering, Georgia Institute of Technology, Atlanta, GA, USA (advisor: Professor Cheng Zhu)
2007 M.S., Chemical Engineering, Georgia Institute of Technology, Atlanta, GA (USA)
2003 M.S., Biomedical Engineering, Institute of Mechanics, Chinese Academy of Sciences and Chongqing University (Joint Program), Beijing, China
2000 B.S. (with honor), Chemical Engineering, Chongqing University, Chongqing, China
Postdoctoral training:
2009– Department of Microbiology and Immunology, Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA (advisor: Professor Mark M. Davis)
Practical information
- Informed public
- Free
- This event is internal
Organizer
- Prof. Melody Swartz