Department of Physics, Chemistry and Biology (IFM)

One of the strategies that have been used to enhance the immunogenicity of DNA vaccines was co-administration of co-stimulatory molecules such as potential molecular adjuvants. Unlike conventional adjuvants, molecular adjuvants are delivered as plasmid vector along with the vector encoding the antigen of interest.

The TNF receptor superfamily (TNFRSF) consists of approximately 50 membrane and soluble proteins which can modulate cellular function. TNF superfamily ligands (TNFSFL) are costimulatory molecules that have been reported to be involved in dendritic cell (DC) and T cell activation and have also been used as adjuvants in several vaccination studies.

Glucocorticoid induced TNFR related protein ligand (GITRL) is a member of TNFR superfamily that modulates natural and acquired immune response. Expressed in the cell surface of macrophages, dendritic cells, endothelial cells, and B cells, GITRL (TNFSF18/AITRL/TL6) is well known for its interaction with its cognate receptor GITR. GITRL encoded protein has 173 aminoacids and a molecular weight of 20kDa.

It was concluded from a study that GITRL induced signaling is mediated by ERK1/2, which then triggers the activation of the transcription factor NF-ĸB. NF-ĸB controls the expression of several pro-inflammatory mediators such as chemokines and cytokines.

Tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), a novel member of TNFSF has been reported to activate a large number of cellular functions including migration and proliferation TWEAK shares a common feature with GITRL that it plays a vital role in the signaling pathways that involves an activation of the transcription factor NF-ĸB. Secreted in its soluble form as a type II transmembrane protein, TWEAK is a multifunctional cytokine and its signaling involves its high affinity binding with the receptor fibroblast growth factor inducible 14kDa protein (Fn14/TWEAKR).