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Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28

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Abstract

Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. CML28, a recently discovered cancer-testis (CT) antigen from chronic myelogenous leukemia, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A*0201 is one of the most common histocompatibility molecule in Chinese, we aim at identifying CML28 peptides presented by HLA-A*0201. A panel of CML28-derived antigenic peptides was predicted using a computer-based program. Four peptides with highest predicted score were synthesized and tested for their binding affinities to HLA-A*0201 molecule. Then these peptides were assessed for their immunogenicity to elicit specific immune responses mediated by CTLs both in vitro, from PBMCs sourced from four healthy HLA-A*0201+ donors, and in vivo, in HLA-A*0201 transgenic mice. One of the tested peptides, CML28(173–181), induced peptide-specific CTLs in vitro as well as in vivo, which could specifically secrete IFN-γ and lyse major histocompatibility complex (MHC)-matched tumor cell lines endogenously expressing CML28 antigen and CML28(173–181) pulsed Jurkat-A2/Kb cells, respectively. These results demonstrate that CML28(173–181) is a naturally processed and presented CTL epitope with HLA-A*0201 motif and has a promising immunogenicity both in vitro and in vivo. As CML28 is expressed in a large variety of histological tumors besides chronic myelogenous leukemia, we propose that the newly identified epitope, CML28(173–181), would be of potential use in peptide-based, cancer-specific immunotherapy against a broad spectrum of tumors.

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Acknowledgements

This work was supported by National key basic research program of China (2001CB510001) and National Natural Science Foundation of China (No. 30400215, 30490240, 30271284, and 30200277). The authors thank Dr. Jehad Charo a lot for providing Jurkat-A2/Kb cell line. Professor Jing An, Dr. An Chen and Dr. Zhengcai Jia are acknowledged for critically reading the manuscript and for their kind suggestions.

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  1. Institute of Immunology, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, 400038, Chongqing, China

    Jun-Feng Han, Ting-Ting Zhao, Hong-Li Liu, Zhi-Hua Lin, Hui-Ming Wang, Zhi-Hua Ruan, Li-Yun Zou & Yu-Zhang Wu

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  1. Jun-Feng Han
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Correspondence to Yu-Zhang Wu.

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Han, JF., Zhao, TT., Liu, HL. et al. Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28. Cancer Immunol Immunother 55, 1575–1583 (2006). https://doi.org/10.1007/s00262-006-0152-8

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