Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from CML28.
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-gamma 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.
Institute of Immunology, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, 400038, Chongqing, China.
Jun-Feng
JF
Han
Ting-Ting
TT
Zhao
Hong-Li
HL
Liu
Zhi-Hua
ZH
Lin
Hui-Ming
HM
Wang
Zhi-Hua
ZH
Ruan
Li-Yun
LY
Zou
Yu-Zhang
YZ
Wu
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005095:Exoribonucleases / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D063326:Exosome Multienzyme Ribonuclease Complex; D015234:HLA-A Antigens / Q000378:metabolism*; D015789:HLA-A2 Antigen; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C467564:EXOSC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D016601:RNA-Binding Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex