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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

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Abstract

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.

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Acknowledgements

We thank Dr. Medi Adibzadeh, Tübingen, for helping to initiate these studies, Prof. W. Voelter and Dr. Hubert Kalbacher for peptide synthesis and Dr. Martin Deeg for assistance with mass spectrometry. We thank Prof. Jesper Zeuthen for providing class I peptides, Prof. C.A. Müller for HLA typing and Prof. G.A. Müller and Dr. I. Trowbridge for antibodies. We thank the patients who provided blood samples and their physicians for making them available for this study.

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Authors and Affiliations

  1. Section for Transplantation Immunology and Immunohaematology, Second Department of Internal Medicine, Tübingen University Medical School, Tübingen, Germany

    Wolfgang M. Wagner, Qin Ouyang & Graham Pawelec

  2. Zentrum für Medizinische Forschung, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Wolfgang M. Wagner

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  1. Wolfgang M. Wagner
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Correspondence to Wolfgang M. Wagner.

Additional information

This work was supported by the EU (QLRI-CT-2000-01325, ESTDAB), the Mildred Scheel Foundation for Cancer Research (Deutsche Krebshilfe) grant no. 10-1173-Pa3 and the Dieter Schlag Foundation for Research into Diseases of the Blood. The peptide sensitization protocols were developed as part of an EU collaborative project (EUCAPS, contract BMH4-CT98-3058).

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Wagner, W.M., Ouyang, Q. & Pawelec, G. 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. Cancer Immunol Immunother 52, 89–96 (2003). https://doi.org/10.1007/s00262-002-0362-7

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