T cells from DNAM-1 deficient mice display immunological synapse defects that impair anti-tumour immunity (P2009)

Abstract

Abstract DNAX accessory molecule 1 (DNAM-1/CD226) is an adhesion molecule expressed on all CD8+ cytotoxic T cells (CTLs) that acts as an accessory molecule to promote CTL functions such as activation, differentiation, migration and effector function. DNAM-1 interacts with LFA-1, a critical molecule for immunological synapse formation between T cells and antigen presenting cells, and for cytotoxic killing of target/tumour cells. Indeed, mice lacking DNAM-1 display abnormal T cell responses and anti-tumour activity; however, the mechanism involved is not well understood. Here, we investigate the immunological synapse between OT1 DNAM-1 deficient T cells and antigen presenting cells, and show that DNAM-1 deficiency results in reduced proliferation and expansion of T cells in response to antigen presentation, which correlates with a decrease in cytokine production. Furthermore, we demonstrate that activated OT1 DNAM-1 deficient T cells show reduced stable conjugations with tumour cells and decreased recruitment of LFA-1 and lipid rafts to the immunological synapse, which correlates with reduced killing in vitro. This polarity defect may explain why DNAM-1 deficient mice cannot clear tumours in vivo and highlights the importance of the immunological synapse in T cell mediated anti-tumour immunity.