Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9; 22) (q34; q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be presented by antigen-presenting cells and recognized specifically by human T lymphocytes. We have generated a CD4⁺ T lymphocyte line (NG-1) which recognizes the peptide epitope (GFKQSSKALQR) in association with HLA-DRβ1*0101-02. A comparison of antigen-presenting cells showed that CMRF-44⁺ blood dendritic cell presented a 12mer b3a2 peptide effectively. The b3a2 peptide was able to generate specific primary T-lymphocyte responses in other HLA-DR1 donors. We also show that bcr-abl, b3a2 peptide-specific T-lymphocyte lines proliferate in response to bcr-abl b3a2 containing cell lysates (K562 or CML PBMC derived) but not control (including b2a2 CML PBMC) lysates.