Navigation Links
Carnegie Mellon fluorescent biosensor reveals mechanism critical to immune system amplification
Date:4/23/2012

PITTSBURGHUsing a new fluorescent biosensor they developed, researchers at Carnegie Mellon University have discovered how a key set of immune cells exchange information during their coordinated assault on invading pathogens. The immune cells, called dendritic cells, are harnessed by cancer vaccines and other therapeutics used to amplify the immune system. The finding, published online March 29 in the journal Angewandte Chemie, marks the first time that scientists have visualized how antigens are transferred in the immune system between dendritic cells.

"Knowing the mechanism behind what's going on in these dendritic cells how they are talking to each other in order to amplify the immune response is of fundamental significance," said Marcel P. Bruchez, associate professor of biological sciences and chemistry in the Mellon College of Science.

Dendritic cells are specialized immune cells that search for and capture foreign micro-organisms like bacteria, allergens or viruses. The cells engulf the invading organism and break it down into pieces. The dendritic cell then places these pieces, called antigens, on its cell surface.

When a dendritic cell presents antigens on its surface, it instructs other immune cells to multiply and scour the body in search of the harmful micro-organisms. Dendritic cells also can share antigens with other dendritic cells to boost immune cell activation. While scientists knew that antigens from one dendritic cell could show up in another dendritic cell, they didn't know how those antigens got there.

To determine the precise mechanism by which dendritic cells transfer antigens to each other, the research team used a new pH-biosensor developed at Carnegie Mellon's Molecular and Biosensor Imaging Center (MBIC). The biosensor is made up of two components: a fluorogen activating peptide (FAP), which is genetically expressed in a cell and tagged to a protein of interest, and a dye called a fluorogen, which either glows red or green depending on the pH level of its environment.

"All routes into the cell have characteristic pH profiles," Bruchez said. "Our pH-biosensor allows us to determine whether the tagged protein in this case a surrogate antigen is moving through neutral compartments into the cell, or through acidic compartments into the cell. Those sorts of things determine whether the antigen enters the cell through an active endocytic process, a phagocytic process, or a caveolar uptake process."

In the current study, researchers tagged a surrogate antigen on the surface of a dendritic cell with the FAP. They added the pH sensitive dye, causing the FAP antigen to glow green, an indication of a neutral pH. As the antigen and its bound dye passed to a separate dendritic cell, the antigen/FAP complex glowed red, indicating it used an acidic pathway to enter the new cell. This change in pH from neutral to acidic reveals that antigens are passed between cells through an active endocytic process.

"Once it's nibbled by the acceptor cell, the antigen goes through this endocytic pathway where it can potentially then be reprocessed and re-displayed on the surface of the receptor cell," Bruchez said.

The new biosensor's activity is novel, Bruchez said, because it binds to its target with nanomolar affinity, becomes fluorescently activated, and then is carried into the cell under endocytic conditions, reporting on the pH as it goes. The researchers are hopeful that this technology is the first in a platform of targetable environmental sensors. The current biosensor can read out pH, but this approach could be extended to measure calcium or other ion fluctuations in living cells. According to Bruchez, there are many ways that this basic chemical concept can be extended.


'/>"/>
Contact: Jocelyn Duffy
jhduffy@andrew.cmu.edu
412-268-9982
Carnegie Mellon University
Source:Eurekalert

Related biology news :

1. Carnegie Mellon to receive $900,000 from EPA for brownfields research
2. Carnegie Mellons Philip LeDuc participates in think tank forums
3. Carnegie Mellon developing automated systems to enable precision farming of apples, oranges
4. Carnegies Field and Koshland Elected AAAS Fellows
5. Carnegie Mellon to unveil new sequestration plan
6. Carnegies Arthur Grossman receives Gilbert Morgan Smith medal
7. Carnegies Joe Berry elected Fellow of the American Geophysical Union
8. Carnegies Doug Koshland elected Fellow of the American Academy of Microbiology
9. Carnegies Donald Brown receives lifetime achievement award from Society for Developmental Biology
10. Carnegie Mellon researchers apply new statistical test
11. Carnegie Mellons Kris Matyjaszewski recieves EPAs Presidential Green Chemistry Challenge Award
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... 24, 2017 Research and Markets has announced ... Analysis & Trends - Industry Forecast to 2025" report to ... The ... a CAGR of around 15.1% over the next decade to reach ... analyzes the market estimates and forecasts for all the given segments ...
(Date:3/22/2017)... , March 21, 2017 Vigilant Solutions ... serving law enforcement agencies, announced today the appointment of ... director of public safety business development. Mr. ... enforcement experience, including a focus on the aviation transportation ... most recent position, Mr. Sheridan served as the Aviation ...
(Date:3/9/2017)... March 9, 2017 4Dx has publicly released ... Imaging Workshop at the University of Pennsylvania. Founder and ... deliver the latest data to world leaders in lung ... together leaders at the forefront of the industry to ... "The quality of the imaging is ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... New York , March 23, 2017 ... blood plasma products and derivatives market is fragmented due to the presence ... players, such as Proliant, Thermo Fisher , and Sigma-Aldrich, compete ... leader, these three companies, collectively, held more than 76% of this ... ...
(Date:3/22/2017)... ... March 22, 2017 , ... ... tissue regeneration from small lab samples to full-size tissues, bones, even whole organs ... a vascular system that delivers blood deep into the developing tissue. , ...
(Date:3/22/2017)... March 22, 2017   iSpecimen ®, the ... Doctors Pathology Service (DPS), a full-service anatomic ... the United States , has joined a ... Information Network (DHIN) to make human biospecimens and ... The novel program, announced in 2015 as a collaboration ...
(Date:3/22/2017)... March 22, 2017   VWR ... of product and service solutions to laboratory ... has acquired EPL Archives, Inc., an international ... the entire regulated product research, development and ... storage and ancillary services. EPL Archives is ...
Breaking Biology Technology: