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Clonal T‐cell response against autologous pleomorphic malignant fibrous histiocytoma antigen presented by retrieved HLA‐A*0206
Author(s) -
Kimura Shigeharu,
Kozakai Yuriko,
Kawaguchi Satoshi,
Tsukahara Tomohide,
Ida Kazunori,
Murase Masaki,
Matsumura Tadaki,
Kaya Mitunori,
Torigoe Toshihiko,
Wada Takuro,
Sato Noriyuki,
Yamashita Toshihiko
Publication year - 2008
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20497
Subject(s) - antigen , ctl* , human leukocyte antigen , pathology , medicine , biology , immunology , cd8
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. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:271–278, 2008