IDENTIFICATION OF A COSTIMULATORY MOLECULE RAPIDLY INDUCED BY CD40L AS CD44H

The interaction between CD40 ligand and CD40 is critical for activatio n of T and B cells in vivo. We have recently demonstrated that this in teraction rapidly induces a novel costimulatory activity distinct from B7 and independent of CD28. To study the molecular basis of the costi mulatory activity, we have produced a novel monoclonal antibody, TM-1, that binds an 85-kilodalton costimulatory molecule rapidly induced by CD40L. Expression cloning reveals that TM-1 binds CD44H. CD44H expres sed on Chinese hamster ovary cells has potent costimulatory activity f or clonal expansion of T cells isolated from both wild-type mice and t hose with a targeted mutation of CD28. Thus, CD44H costimulates T cell proliferation by a CD28-independent mechanism. These results revealed that CD44H is a costimulatory molecule rapidly induced by CD40L.