The abl/bcr gene product as a novel leukemia-specific antigen: peptides spanning the fusion region of abl/bcr can be recognized by both CD4+ and CD8+ T lymphocytes

被引:0
作者
Wolfgang M. Wagner
Qin Ouyang
Graham Pawelec
机构
[1] Tübingen University Medical School,Section for Transplantation Immunology and Immunohaematology, Second Department of Internal Medicine
[2] University of Tübingen,Zentrum für Medizinische Forschung
来源
Cancer Immunology, Immunotherapy | 2003年 / 52卷
关键词
Chronic myelogenous leukemia; Tumor antigens; abl/bcr; bcr/abl; T lymphocytes;
D O I
暂无
中图分类号
学科分类号
摘要
Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation leading to the Philadelphia chromosome. Two fusion genes are created by this translocation: bcr/abl and abl/bcr. The fusion regions of both translocation products are unique and strictly limited to leukemia cells, giving rise to potential tumor-specific antigens. Although several studies on the immunogenicity of peptides spanning the bcr/abl fusion region have been reported, little is known about the corresponding reciprocal translocation product abl/bcr. Here we report that synthetic peptides representing the fusion region of the abl/bcr forms a1bb3 and a1bb4 can be specifically recognized by HLA-A2-restricted cytotoxic T lymphocytes from healthy donors. Furthermore, HLA-matched a1bb3-expressing CML cells can be recognized by a1bb3-specific HLA-A2-restricted T cells, indicating natural processing and presentation of abl/bcr protein by leukemia cells. Moreover, a 19-mer peptide encompassing this class I-binding sequence also elicited a1bb3-specific class II-restricted T-cell responses. Thus, both class I- and class II-restricted T-cell responses can be stimulated in healthy donors by abl/bcr peptides in vitro. Because abl/bcr is expressed in the majority of CML patients, it may represent a highly leukemia-specific antigen with potential use in immunotherapy.
引用
收藏
页码:89 / 96
页数:7
相关论文
共 37 条
[1]  
Goldman undefined(2001)undefined Blood 98 2039-undefined
[2]  
Gorre undefined(2002)undefined Curr Opin Hematol 9 303-undefined
[3]  
Smit undefined(1998)undefined Proc Natl Acad Sci U S A 95 10152-undefined
[4]  
Deininger undefined(2000)undefined Blood 96 3343-undefined
[5]  
Faderl undefined(1999)undefined N Engl J Med 341 164-undefined
[6]  
Bocchia undefined(1996)undefined Blood 87 3587-undefined
[7]  
Pawelec undefined(1996)undefined Blood 88 2118-undefined
[8]  
Melo undefined(1993)undefined Blood 81 158-undefined
[9]  
Berke undefined(2000)undefined Leukemia 14 419-undefined
[10]  
Wagner undefined(2002)undefined Leukemia 16 2341-undefined