Identification of HLA-A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung.
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 Valpha5 and Vbeta7 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.
Sugaya
Masakazu
M
The Second Department of Surgery, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan. sugaya@med.uoeh-u.ac.jp
Takenoyama
Mitsuhiro
M
Shigematsu
Yoshiki
Y
Baba
Tetsuro
T
Fukuyama
Takashi
T
Nagata
Yoshika
Y
Mizukami
Makiko
M
So
Tetsuya
T
Ichiki
Yoshinobu
Y
Yasuda
Manabu
M
So
Tomoko
T
Hanagiri
Takeshi
T
Sugio
Kenji
K
Yasumoto
Kosei
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D018287:Carcinoma, Large Cell / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D015234:HLA-A Antigens / Q000032:analysis*; D059871:HLA-A24 Antigen; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D008840:Microfilament Proteins; C517893:NYGFQIHTK; D009842:Oligopeptides; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C425471:TRIOBP protein, human