ROLE OF THEMIS IN REGULATING THE SIGNALLING AND FUNCTIONS OF PERIPHERAL T CELLS

Abstract

The development of self-tolerant yet foreign-reactive T cell repertoire is important to avoid autoimmunity. This tolerance is achieved during positive and negative selection stages of T cell development. Themis, a T cell lineage-specific protein, helps in positive selection. Until now, studies have mainly highlighted the role of Themis in development of T cells in the thymus. This project focuses on elucidating the role of Themis in mature T cells.

For this, we developed of an Acute Themis Deletion Model which helped us to overcome the experimental problems associated with other models, developed to study the role of Themis in the periphery. We have shown how Themis influences T cell activation, signaling, effector functions and metabolism in T cells. Additionally, we have also been able to devise a high throughout imaging flow cytometry-based protocol to carry out a preliminary analysis of the energetics of T cells (glycolysis or oxidative phosphorylation) through screening the mitochondrial parameters in these cells.