J. Exp. Med., Volume 187, Number 3, February 2, 1998 277-288

A Gene Encoding Antigenic Peptides of Human Squamous Cell Carcinoma Recognized by Cytotoxic T Lymphocytes

By Shigeki Shichijo,^* Masanobu Nakao,^§ Yasuhisa Imai,^* Hideo Takasu,^* Mayumi Kawamoto,^* Fumihiko Niiya, Damu Yang,^§ Yuji Toh, Hideaki Yamana, and Kyogo Itoh^*§

From the ^* Departments of Immunology and  the Department of Surgery, Kurume University School of Medicine, and the ^§ Division of Cancer Vaccine, Kurume University Research Center for Innovative Cancer Therapy, Kurume, 830, Japan

Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601-restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating 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 cancers 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 peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601⁺ epithelial cancer patients.

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