Poster Presentation Melbourne Protein Group Student Symposium 2013

Characterization of two Novel TNF Receptor Superfamily Members: Relt and Troy (#10)

Tanu S Arora 1 , Joanne L Casey 1 , Amelia Johnston 1 , John Silke 1 2 , Michael Foley 1
  1. The Co-operative Research Centre for Biomarker Translation, Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia
  2. Walter and Eliza Hall Institute of Medical Research, Department of Biochemistry, Melbourne, Victoria, Australia
Receptor expressed in lymphoid tissues (RELT) is a type I transmembrane receptor member of the TNF receptor superfamily (TNFRSF) of cytokines. The extracellular domain of RELT is composed of a single, cysteine-rich domain (CRD) possessing significant homology to other members of TNFRSF. RELT is expressed at high levels in haematological tissues and immune cell lines (T cells, B cells and myeloid cell lines). It is also seen to express in abundance in leukaemia and lymphomas. So RELT could be a potential biomarker for autoimmune diseases.

Another TNF receptor under investigation is TROY, which is a member of the EDAR (EDA) receptor (EDAR) subfamily. TROY is a type I transmembrane receptor of the TNRSF which has three characteristic cysteine rich domain in an extracellular domain. TROY is widely expressed in skin during embryogenesis but in adults expression is restricted to hair follicles and brain. TROY mRNA exclusively expressed in the epithelium of many tissues, and moderately expressed in the heart, lung, and liver but not the spleen. The mRNA level is strongly upregulated in melanoma (primary and metastatic) but not in normal melanocytes, so it could be a novel melanoma biomarker and potential therapeutic target.

It is not known what ligands exist for the TNF receptors TROY and RELT, and currently there are no publications of any known human or mouse TNF ligands binding to these receptors.

I have identified the binders to TROY and RELT from a human Fab phage-displayed library and iBODY (humanized analogues of shark antibodies) library respectively as an alternative to monoclonal antibody production. The antibody fragments will be further characterised for their interaction with TNF receptors and for their ability to act as agonists or antagonists to TNF receptor signalling in cell based assays. The long term aim is to generate potential lead compounds for use in therapies against diseases where TNF receptors play an important role.