1. Identification of HLA class I–restricted tumor-associated antigens in adult T cell leukemia cells by mass spectrometric analysis
- Author
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Kawahara, Masahiro, Hori, Toshiyuki, Matsubara, Yasushi, Okawa, Katsuya, and Uchiyama, Takashi
- Subjects
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PROTEINS , *PEPTIDES , *T cells , *LYMPHOCYTES - Abstract
Objective: In this study, we attempted a comprehensive analysis of MHC class I–bound peptides in adult T cell leukemia (ATL) cells in order to identify as many tumor-associated antigens (TAAs) as possible that could be used for CTL-based immunotherapy. Methods and Results: Using mass spectrometry combined with reversed-phase liquid chromatography, we could sequence 188 HLA class I–restricted candidate peptides from three ATL-derived cell lines. In accordance with the restrained expression of HTLV-I viral RNA in these cell lines, there were no HTLV-I-encoded peptides among these candidates. Based on the differential expression between ATL cells and normal CD4+ T cells, we selected 10 novel peptides as T cell epitopes of overexpressed source proteins. RT-PCR analysis revealed that 5 source proteins including PRAME, a known tumor-testis antigen, were highly expressed in the majority of 16 ATL cases. Furthermore we could induce PRAME-specific CTLs in vitro from an HLA-B62+ healthy donor that showed specific cytotoxicity against HLA-B62+ PRAME+ ATL cells. Conclusion: These results demonstrate that comprehensive analysis of HLA class I–bound peptides by mass spectrometry is useful for identification of TAA-derived peptides in ATL. Considering that expression patterns of leukemia/lymphoma-associated antigens vary from case to case, this approach appears to be suitable for the tailor-made immunotherapy of hematological malignancies. [Copyright &y& Elsevier]
- Published
- 2006
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