MODULATING T CELL RECEPTOR SIGNALLING IN RESPONSE TO SUBOPTIMAL AGONIST PEPTIDE-MHC COMPLEX

Abstract

There are lots of instances where the agonist signal is suboptimal. In this thesis, several strategies and gene functions have been studied to try to optimize T cell responses to suboptimal agonists by modulating T cell receptor signalling. The first part is to study coagonism in human T cells. We found that non-stimulatory-peptide-MHC could be used as coagonist to enhance human T cell response to HBV antigens. Coagonism in human T cell required CD8 binding but not TCR binding to the coagonist pMHC. The second part of the thesis focus on a gene called Themis in regulating TCR signalling strength. There is quite high-level expression of Themis in mature T cells. We found that the TCR signalling strength might not be largely affected in Themis conditional knockout mice lymphocytes, but there is less cytokine production. There are also more TCR downregulation in Themis conditional knockout lymphocytes.