Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells
Two signals are necessary for a successful T cell activation; interaction of the T cell receptor (TCR) with the major histocompatibility complex II (MHC) antigens on the antigen presenting cells (APC) and interaction of the CD28 receptor on the lymphocyte with B7 proteins presented by the APC.  The role of CD28 receptor in T cell activation remains poorly understood, with an ongoing debate on whether it amplifies TCR based signal, drives unique changes in the cell or whether it is neede at all for certain T cell subsets activation. Self-recognition by TCR can lead to autoimmunity, highlighting the importance to better study these pathways using genomics tools. We aimed to decouple the T cell activation signals in order to better understand their role in immune response. I believe that by joining immunophenotyping with gene expression studies we can elucidate the pathways engaged by CD28 co-stimulation for a successful T cell activation in naive and memory cells. That will also allow us to explore the effect of increasing TCR signal in the differentiation of naive cells. Looking at gene expression variability between individuals, as well as their threshold response to a stimulus, we can gain an insight into the role of genetic variants in activation processes of CD4+ cells.