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Immunobiology

Peptides spanning the junctional region of both the abl/bcr and the bcr/abl fusion proteins bind common HLA class I molecules

Leukemia volume 14, pages 419–426 (2000)Cite this article

Abstract

The Philadelphia (Ph) chromosome, resulting from the t(9;22) translocation, is characteristic of chronic myeloid leukemia (CML). As a result of this translocation, two novel chimeric genes are generated and the bcr/abl and abl/bcr fusion proteins expressed. The bcr/abl fusion mRNA is present in all CML patients, whereas the reciprocal abl/bcr fusion mRNA is detectable in about 80% of the Ph+ CML patients. These fusion proteins may undergo enzymatic degradation in the cytosol and give rise to MHC class I restricted peptide epitopes originating from the junctional regions of the translocation products, which thus may serve as novel tumor specific antigens. Previously, other groups have tested peptides corresponding to the junctional region of the bcr/abl protein for their binding capacity to HLA class I molecules and have identified a few candidate epitopes. Peptides originating from the abl/bcr fusion protein have on the other hand so far been neglected, for no apparent reason. We have now extended these studies to include also the reciprocal abl/bcr translocation product by testing a large panel of synthetic peptides corresponding to the junctional regions of both the abl/bcr and the bcr/abl fusion proteins for their ability to stabilize HLA class I molecules. We find that the abl/bcr translocation product may be an even more important source of CML specific peptide antigens and together the junctional sequences of both these proteins contain peptide sequences which bind efficiently to a number of HLA molecules (HLA-A1, -A2, -A3, -A11, -B7, -B27, -B35) and thus may serve as candidate CML specific tumor antigens.

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Acknowledgements

This work was supported by the Danish Medical Research Council, the Danish Cancer Society, the Novo Nordisk Foundation, the Direktør E Danielsen og Hustru Foundation, Fru Astrid Thaysens Foundation for Medical Research, and the Anders Hasselbalch Foundation against Leukaemia.

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  1. Z Berke and MH Andersen: The first two authors contributed equally to this work

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  1. Institute of Cancer Biology, the Danish Cancer Society, Copenhagen, Denmark

    Z Berke, MH Andersen, J Zeuthen & JS Haurum

  2. The State University Hospital, Copenhagen, Denmark

    M Pedersen

  3. Department of Clinical Immunology, Skejby Hospital, Aarhus, Denmark

    L Fugger

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Berke, Z., Andersen, M., Pedersen, M. et al. Peptides spanning the junctional region of both the abl/bcr and the bcr/abl fusion proteins bind common HLA class I molecules. Leukemia 14, 419–426 (2000). https://doi.org/10.1038/sj.leu.2401703

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