The present invention provides compositions comprising peptidyl inhibitors of CD40L-dependent signalling that are not derived from a natural binding partner of CD40L such as CD40, or from a native CD40-CD40L interface. More particularly, the peptidyl inhibitors of the present invention are derived from natural sources that do not express CD40-CD40L costimulatory pathways. The invention also provides synthetic derivatives and analogs of the peptidyl inhibitors having enhanced binding affinity for CD40L or enhanced inhibitory activity relative to their parent molecules.
