|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|
|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|
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.
|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
|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.|