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Introduction of a Disulfide Bond in the 1 Domain of the H-2K^b Molecule Confers Immunogenicity to the Transfected RMA-S Tumors¹

Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021

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 1 domain of a murine class I molecule, K^b. The expression of the engineered, but not the wild-type, K^b molecules conferred immunogenicity to a nonimmunogenic and antigen presentation-defective tumor cell line, RMA-S. Mice that rejected the engineered K^b-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.

¹ This work was supported by the Howard Hughes Medical Institute.

² To whom requests for reprints should be addressed, at Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461.

Received 6/ 7/94. Accepted 7/21/94.