In accordance with the present invention, there are provided novel Death Domain (DD), Death Effector Domain (DED) and NB-ARC domain proteins. The invention also provides nucleic acid molecules encoding DD, DED and NB-ARC domain proteins, vectors containing these nucleic acid molecules and host cells containing the vectors. The invention also provides antibodies that can specifically bind to invention DDs, DEDs or NB-ARC domains. Such DDs, DEDs and NB-ARC domains and/or anti-DD, anti-DED or anti-NB-ARC domain antibodies are useful for discovery of drugs that suppress infection, autoimmunity, inflammation, allergy, allograft rejection, sepsis, and other diseases.