CD46, a new costimulatory molecule for T cells, that induces p120(CBL) andLAT phosphorylation

The widely expressed transmembrane molecule CD46 is the complement regulato ry receptor for C3b as well as the receptor for several pathogens. Beside i ts binding functions, CD46 is also able to transduce signals. We showed tha t CD46 aggregation on human T cells induces p120(CBL) and linker for activa tion of T cells (LAT) phosphorylation, These two proteins are adaptor prote ins known to regulate TCR signaling. p120(CBL) is a complex adaptor protein involved in negatively regulating signaling events, whereas LAT is a trans membrane adaptor protein found in glycolipid enriched microdomains essentia l for T cell activation. Therefore, we investigated if a CD46/TCR costimula tion would affect T cell activation. Indeed, CD46/CD)3 costimulation strong ly promotes T cell proliferation. Therefore, we propose that CD46 acts as a potent costimulatory molecule for human T cells.