The present invention relates to therapeutical uses of non-classical major histocompatibility complex (MHC), also known as MHC class lb molecules in combination with defined peptides. The invention more specifically relates to targeted immunomodulatory effects of defined peptides in combination with proteins comprising one or more domains of a non-classical MHC class lb molecule or in combination with molecules that interfere with the interaction of MHC class lb molecules and their receptors. The invention also relates to methods of producing such proteins, pharmaceutical compositions comprising the same, as well as their uses for treating medical conditions in which antigen-specific immune reactions are beneficial, including cancer and infectious diseases, or harmful, including autoimmune diseases, organ/tissue rejection, immune reactions towards pharmaceutical compounds or reproductive disorders. Moreover, as the invention reveals a novel mode of action for MHC class lb molecules during antigen-specific tolerance induction, it also relates to methods for interfering with this mechanism in situation where induction of antigen-specific immune tolerance is wanted, but physiologically prevented by said mechanism.
