Non-conventional human T lymphocyte subsets likely contribute to immune surveillance of cellular distress, thanks to their ability to recognize conserved determinants that are modulated in contexts of inflammation, infection or cancer.
The group aims at pursuing the characterization of antigens recognized by human γδ T lymphocyte subsets as well as their functions elicited by human stressed cells (eg, infected/tumor cells). The group evidenced the mandatory role played by the butyrophilin CD277, not only in tumor cell recognition by human Vγ9Vδ2 T cells, but also in their activation induced by soluble PAg or by target cells treated with aminobisphophonates. These results indicated that PAg act intracellularly in target cells and their direct interactions with the B30.2 domain of the BTN3A1 isoform, which are next sensed by human Vγ9Vδ2 T cells. The analysis are achieved by combining molecular biology, biochemistry and high-resolution microscopy (eg, TIRF, STORM, PLA) approaches together with immunological tools to decipher the regulation of functions and membrane dynamics of BTN3A1 (eg, inside-out mechanisms) and the respective contribution of each molecular partner in this particular T cell antigenic activation process.
On a more applied side, the group has developed various in vivo models of human orthotopic tumors (eg, brain, ovary) to evaluate several anti-tumor efficiency and feasibility parameters of γδ T lymphocyte-based immunotherapies in immunodeficient NSG mice (breeding). These informations are exploited for the design of improved immunotherapies in patients (eg, glioblastoma).