SOLUBLE MHC MOLECULES TO INDUCE ALLOGRAFT TOLERANCE

POLYMORPHIC CELL-SURFACE MOLECULES ENCODED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) OF VERTEBRATES ARE RESPONSIBLE FOR INITIATING A NUMBER OF PHYSIOLOGICAL RESPONSES WHEN THESE ANTIGENS ARE RECOGNIZED AS "NONSELF" BY THE IMMUNE SYSTEM. THE REJECTION OF DONOR TISSUE GRAFTS BY RECIPIENTS WHOSE MHC MOLECULES ARE DISSIMILAR PRESENTS A MAJOR OBSTACLE IN THE FIELD OF TRANSPLANTATION. WHILE ATTEMPTS TO HELP INDIVIDUALS TOLERATE THESE CELL-SURFACE ANTIGENS HAVE MET WITH CONSIDERABLE DIFFICULTY,THE EASE OF INDUCING TOLERANCE TO SOLUBLE NONSELF PROTEINS HAS BEEN FIRMLY ESTABLISHED. THUS, BIOGEN RESEARCH CORPORATION PROPOSES TO GENETICALLY ENGINEER THESE MHC MOLECULES TO BE EXPRESSED AS SECRETED FORMS SO THEY CAN BE PURIFIED EASILY. THE ABILITY OF THESE MOLECULES TO EXPERIMENTALLY INDUCE TOLERANCE TO ALLOGRAFTS IN MICE WILL BE INVESTIGATED IN PHASE II STUDIES. IF SUCCESSFUL, THESE METHODS CAN BE APPLIED TO THE HUMAN SYSTEM.