Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation

The widely expressed transmembrane molecule CD46 is the complement regulatory receptor for C3b as well as the receptor for several pathogens. Beside its binding functions, CD46 is also able to transduce signals. We showed that CD46 aggregation on human T cells induces p120CBL and linker for activation of T cells (LAT) phosphorylation. These two proteins are adaptor proteins known to regulate TCR signaling. p120CBL is a complex adaptor protein involved in negatively regulating signaling events, whereas LAT is a transmembrane adaptor protein found in glycolipid-enriched microdomains essential for T cell activation. Therefore, we investigated if a CD46/TCR costimulation would affect T cell activation. Indeed, CD46/CD3 costimulation strongly promotes T cell proliferation. Therefore, we propose that CD46 acts as a potent costimulatory molecule for human T cells.