ALK2/3 recruitment to the immunological synapse is required for T cell activation and death

Antigen recognition by TCR triggers T cell activation and activation-induced cell death (AICD). We identified that the BMP receptors ALK2 and ALK3 were interdependently required for induction of a subset of effector genes and AICD in activated T cells, independent of their BMP ligands. Upon T cell activation, ALK2/3 were recruited to the immunological synapse and phosphorylated by PKC-θ at the conserved T203, resulting in their enhanced kinase activities. The activated ALK2/3, in the absence of BMP, phosphorylated SMAD1/5 at S57, which is reciprocally antagonistic to BMP-induced phosphorylation of SMAD1/5 at S463/465. The S57-phosphorylated SMAD1/5 associated with c-Fos to induce effector genes upon T cell activation. Disruption of Alk2 in T cells attenuated T cell-mediated immunity to Listeria, whereas blocking BMPs enhanced host defense to Listeria in WT but not Alk2-deficient mice. Our findings suggest that the BMP-independent ALK2/3-SMAD1/5 axis plays essential roles in T cell activation and AICD, which is reciprocally antagonistic with BMP-triggered inhibition of T cell-mediated immunity.