Clonal T-cell response against autologous pleomorphic malignant fibrous histiocytoma antigen presented by retrieved HLA-A*0206.
Towards the goal of identifying tumor-rejection antigens on eradicated tumors in bone and soft tissue sarcomas, we evaluated the immune response against antigens presented by lost HLA class I molecules. Tumor specimens and peripheral blood samples were obtained from a 70-year-old woman with pleomorphic malignant fibrous histiocytoma. Over 1-year culture, a tumor cell line (MFH2004) was established. A B-cell line infected with Epstein-Barr virus (B2004-EBV) was developed from the blood samples. HLA genotypes of B2004-EBVcells were A*0206/2402, B*4006/4601, and C*0102/0801, whereas MFH2004 cells were defective for A*0206, B*4006, and C*0102. Loss of HLA-A2 expression was also proved immunohistochemically in the primary tumor tissues. Lost HLA-A2 in MFH2004 cells was retrieved by transfection of HLA-A*0206 cDNA to develop MFH2004-A2. Attempts to induce CTLs by mixed culture with autologous T cells and MFH2004 cells resulted in failure. In contrast, those with MFH2004-A2 induced CTL clones CTL2004-c6 and CTL2004-c17. These CTL clones specifically killed MFH2004-A2 but not MFH2004 or B2004-EBV in an HLA-A2-restricted manner. These findings suggest that CTL2004-c6 and CTL2004-c17 recognize autologous tumor-rejection antigens presented by HLA-A*0206, which may have been expressed by tumor cells that had been eradicated by the host's immunosurveillance system.
Kimura
Shigeharu
S
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
Kozakai
Yuriko
Y
Kawaguchi
Satoshi
S
Tsukahara
Tomohide
T
Ida
Kazunori
K
Murase
Masaki
M
Matsumura
Tadaki
T
Kaya
Mitunori
M
Torigoe
Toshihiko
T
Wada
Takuro
T
Sato
Noriyuki
N
Yamashita
Toshihiko
T
D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry; D001324:Autoantigens / Q000737:chemistry; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005838:Genotype; D006680:HLA Antigens; D015234:HLA-A Antigens / Q000737:chemistry*; D015789:HLA-A2 Antigen; D004854:Herpesvirus 4, Human / Q000378:metabolism; D051677:Histiocytoma, Malignant Fibrous / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection
D000951:Antigens, Neoplasm; D001324:Autoantigens; D018076:DNA, Complementary; D006680:HLA Antigens; D015234:HLA-A Antigens; C526286:HLA-A*02:06 antigen; D015789:HLA-A2 Antigen