A GENE ENCODING ANTIGENIC PEPTIDES OF HUMAN SQUAMOUS-CELL CARCINOMA RECOGNIZED BY CYTOTOXIC T-LYMPHOCYTES

Except for melanomas, tumor antigens recognized by cytotoxic T lymphoc ytes (CTLs) are yet unidentified. We have identified a gene encoding a ntigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)-A2601-restricted CTLs. This showed no similarity to known sequences, and encoded two (1 25- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leuc ine zipper motif was expressed in the nucleus of the majority of proli ferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other canc ers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the pept ides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein a nd this nonapeptide (KGSGKMKTE) may be useful for the specific immunot herapy of HLA-A2601(+) epithelial cancer patients.