Fluorescent Biosensor Reveals Immune System Response

Apr 25, 2012 | Contact Author | By: Rachel Grabenhofer
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Title: Fluorescent Biosensor Reveals Immune System Response
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Researchers at Carnegie Mellon University have discovered how immune cells exchange information using a new fluorescent biosensor developed at the university. This discovery was published online on March 29, 2012, in the journal Angewandte Chemie, and according to the university is the first time that scientists have visualized how antigens are transferred in the immune system between dendritic cells.

According to a university press release, dendritic cells capture and engulf foreign microorganisms like bacteria, allergens or viruses and break them down into pieces or antigens that are used to instruct other immune cells to multiply and search the body for more of the same micro-organisms. While scientists knew the antigens can be shared between dendritic cells to boost immune cell activation, it was unclear how the antigens were transferred.

To determine this mechanism, researchers used a new pH-biosensor developed at Carnegie Mellon’s Molecular and Biosensor Imaging Center (MBIC). The sensor consists of 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 glows red or green depending on the pH level of its environment. Researchers tagged a surrogate antigen to a dendritic cell with the FAP and added the pH-sensitive dye, causing the FAP antigen to glow green—indicating a neutral pH. As the antigen and its bound dye passed to a separate dendritic cell, however, the antigen/FAP complex glowed red, indicating an acidic pathway was used 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.

According to Marcel P. Bruchez, associate professor of biological sciences and chemistry in the Mellon College of Science, the biosensor’s activity is novel because it binds to its target with nanomolar affinity, becomes fluorescently activated, and 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, noting that while the current biosensor can read out pH, it could be extended to measure calcium or other ion fluctuations in living cells.

As the personal care industry searches for new cellular pathways to moderate inflammation, such as for anti-aging benefits, or to detect the efficacy of new cosmetic actives, novel techniques such as these may prove useful especially in the interest of claims substantiation.