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Identification of HLA‐A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung

2006; Wiley; Volume: 120; Issue: 5 Linguagem: Inglês

10.1002/ijc.22396

1097-0215

Masakazu Sugaya, Mitsuhiro Takenoyama, Yoshiki Shigematsu, Tetsuro Baba, Takashi Fukuyama, Yoshika Nagata, Makiko Mizukami, Tetsuya So, Yoshinobu Ichiki, Manabu Yasuda, Tomoko So, Takeshi Hanagiri, Kenji Sugio, Kosei Yasumoto,

T-cell and B-cell Immunology

Abstract The aim of the present study was to elucidate the tumor‐specific cellular immunological responses occurring in a patient with large cell carcinoma of the lung who had no evidence of recurrence following surgical resections of both a primary lung lesion and a metastatic adrenal lesion. We analyzed an autologous tumor‐specific cytotoxic T lymphocytes (CTL clone F2b), which were HLA‐A*2402 restricted from regional lymph node lymphocytes. The F2b possessed T cell receptor (TCR) using the Vα5 and Vβ7 gene segment. The existence of precursor CTL (pCTL) against autologous tumor cells (A904L) was analyzed using CTL clone‐specific PCR. Lymphocytes with the same TCR as F2b were detected in the primary tumor tissue, regional lymph node and the peripheral blood collected from the patient 3 years after the operation. Using the F2b, we identified a cDNA clone encoding the tumor antigen using cDNA expression cloning method. The gene was found to encode splicing variant of the Tara gene. Finally, we identified the 9‐mer Ag peptide, using constructions of mini‐genes. The F2b recognized 3 out of 7 HLA‐A24 positive allogeneic tumor cell lines and in 1 out of 7 HLA‐A24 negative allogeneic tumor cell lines when transfected with HLA‐A24. This peptide is therefore considered to be potentially useful for performing specific immunotherapy in a significant proportion of lung cancer patients bearing HLA‐A24. © 2006 Wiley‐Liss, Inc.