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

Citation
Z. Berke 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(3), 2000, pp. 419-426
Citations number
60
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA
ISSN journal
08876924 → ACNP
Volume
14
Issue
3
Year of publication
2000
Pages
419 - 426
Database
ISI
SICI code
0887-6924(200003)14:3<419:PSTJRO>2.0.ZU;2-E
Abstract
The Philadelphia (Ph) chromosome, resulting from the t(9;22) translocation, is characteristic of chronic myeloid leukemia (CML), As a result of this t ranslocation, two novel chimeric genes are generated and the bcr/abl and ab l/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 a bout 80% of the Ph+ CML patients. These fusion proteins may undergo enzymat ic degradation in the cytosol and give rise to MHC class I restricted pepti de epitopes originating from the junctional regions of the translocation pr oducts, 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 an d have identified a few candidate epitopes, Peptides originating from the a bl/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 rec iprocal abl/bcr translocation product by testing a large panel of synthetic peptides corresponding to the junctional regions of both the abl/bcr and t he bcr/abl fusion proteins for their ability to stabilize HLA class I molec ules. We find that the abl/bcr translocation product may be an even more im portant source of CML specific peptide antigens and together the junctional sequences of both these proteins contain peptide sequences which bind effi ciently to a number of HLA molecules (HLA-A1, -A2, -A3, -A11, -B7, -B27, -B 35) and thus may serve as candidate CML specific tumor antigens.