Introduction of a disulfide bond in the alpha 1 domain of the H-2Kb molecule confers immunogenicity to the transfected RMA-S tumors.

Abstract

The use of major histocompatibility complex class I genes is an emerging approach for the immunotherapy of human cancer. The conformational stability of class I molecules is important for their immunologic recognition. We have engineered a disulfide bond in the alpha 1 domain of a murine class I molecule, Kb. The expression of the engineered, but not the wild-type, Kb molecules conferred immunogenicity to a nonimmunogenic and antigen presentation-defective tumor cell line, RMA-S. Mice that rejected the engineered Kb-transfected RMA-S cells developed a long-lived antitumor immune response. These data indicate the possibility of genetically engineering class I molecules to improve their therapeutic potential.