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Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region
Liu Ying; Zhu Ping; Hu Ya-mei
关键词leukemia, B-cell, acute immunoglobulin heavy chain cytotoxic T lymphocyte peptide
刊名CHINESE MEDICAL JOURNAL
2007-04-20
120期:8页:652-657
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]CANCER-IMMUNOTHERAPY ; CLASS-I ; LYMPHOMA ; VACCINATION ; REPERTOIRE ; RESPONSES ; DATABASE ; VACCINES
英文摘要

Background Immunoglobulin heavy chain variable region (IgHV) is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV protein vaccines against lymphoma have demonstrated induction of tumor-specific cytotoxic T lymphocyte (CTL) responses. However, complementary determining regions-based individual vaccines have disadvantages for wide clinical application. Although a recent study demonstrated that immunogenic peptides are derived from framework regions (FR) shared among patients with B-cell lymphoma, how to choose the appropriate peptides for each patient is still unsolved. The aim of this study was to investigate whether immunoglobulin heavy chain FR-derived peptides shared in each IgHV family are potential CTL epitopes presented by B-cell acute lymphoblastic leukemia (B-ALL). Such CTL epitopes might be beneficial to shifting vaccination strategies against B-ALL from individual specificity to family specificity.

Methods Seven IgHV gene families were amplified respectively by PCR and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied in analyzing characteristics of sequences available and predicting HLA-A*0201-restricted CTL epitopes for each IgHV family. An antigen-specific T cell expansion system was used to generate peptide-specific CTLs. The cytotoxicity of CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay.

Results Complete IgHV rearrangements were identified in all of the 71 B-ALL cases. All of 40 sequences available showed >=-98% homology with the nearest germline IgHV genes, indicating IgHV genes in B-ALL of germline nature. Twelve nonapeptides of high HLA-A*0201-binding scores were obtained from 26 productive IgHV protein sequences. Ten (83%) of the peptides were located in FR1 and FR3 shared among the corresponding IgHV family. CTLs specific for the peptide QLVQSGAEV located in FR1 (3-11) shared among the IgHV1 family could be successfully generated from peripheral blood mononuclear cells of two HLA-A*0201 + healthy donors in vitro and were capable of killing HLA-matched B-ALL cell clones belonging to the IgHV1 family.

Conclusion Anti-B-ALL CTLs against immunoglobulin heavy chain FR-derived peptides have family-specific cytotoxicity.

语种英语
WOS记录号WOS:000246165000008
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58215
专题北京大学第一临床医学院_血液内科
作者单位1.Gen Hosp Peoples Liberat Army, Dept Pediat, Beijing 100853, Peoples R China
2.Peking Univ, Hosp 1, Dept Hematol, Beijing 100034, Peoples R China
3.Capital Univ Med Sci, Beijing Childrens Hosp, Dept Hematol, Beijing 100045, Peoples R China
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Liu Ying,Zhu Ping,Hu Ya-mei. Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region[J]. CHINESE MEDICAL JOURNAL,2007,120(8):652-657.
APA Liu Ying,Zhu Ping,&Hu Ya-mei.(2007).Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region.CHINESE MEDICAL JOURNAL,120(8),652-657.
MLA Liu Ying,et al."Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region".CHINESE MEDICAL JOURNAL 120.8(2007):652-657.
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