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Dual Recognition of a Human Cytotoxic T-Cell Clone for Melanoma Antigens¹

Departments of Tumor Biology [H. K., J. A., H. N., A. O., M. Ta.] and Organ Transplantation [S. N., Y. B.], Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan; Department of Immunology, National Children's Medical Research Center, Tokyo 154, Japan [J. A., T. K.]; Department of Immunology, School of Medicine, Kitasato University, Sagamihara, Kanagawa 228, Japan [F. O., M. Ts.]; Department of Dermatology, School of Medicine, Shinshu University, Matsumoto, Nagano 320, Japan [T. S.]; and Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710 [T. L. D., Z. A-W.]

It is well known that tumor-specific CTLs have a crucial role in the elimination of tumors and that different CTL populations recognize tumor antigens in MHC-restricted and MHC-unrestricted manners. We have established two ß CTL clones that recognize melanoma antigens in both human lymphocyte antigen (HLA)-A2-restricted and HLA-unrestricted manners. Flow cytometry analysis showed that these CTL clones carry CD3, CD8, and ß T-cell receptor (TCR) and express low levels of CD56. In contrast, these CTL clones do not express CD16, indicating that they do not contain natural killer cells. TCR analysis of these CTL clones using an anchored PCR method revealed that each clone carries a single ß TCR. Both CTL clones contained the same V and Vß gene segments although they carried different J and Jß gene segments. Taken together, these results confirm that CTL clones that carry a single ß TCR recognize melanoma antigens in both HLA-A2-restricted and HLA-unrestricted manners. It is strongly suggested that the dual recognition of these CTL clones for the melanoma antigens is mediated by TCRs. The novel mechanism for antitumor immunity by these CTLs may be important in the effective elimination of tumors in vivo.

¹ This study was supported by a Grant-in-Aid for Scientific Research in Priority Areas from the Ministry of Education, Science, Sports, and Culture, and a grant for a Comprehensive New 10-Year Strategy of Cancer Control from the Ministry of Health and Welfare, the Government of Japan.

² Present address: Department of Dermatology, School of Medicine, Shinshu University, Matsumoto, Nagano 320, Japan.

³ To whom requests for reprints should be addressed.

Received 12/12/95. Accepted 3/19/96.

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