BCR/ABL-specific peptides KQSSKALQR to HLA-A*0301 and GFKQSSKAL to HLA-B*0801. Proteasomal digestion showed cleavage sites leading to KQSSKALQR but not to GFKQSSKAL. Using mass spectrometry KQSSKALQR

Chronic myeloid leukemia (CML) is a malignant disease caused by dysregulation of a pluripotent hematopoietic precursor cell. CML is characterized by the Philadelphia chromosome, containing the t(9;22) translocation, resulting in the chimeric BCR/ABL oncogene. This translocation has been found to be essential and sufficient for the development of CML. Depending on the exons of the BCR and ABL genes involved in the translocation, several variants of the fusion gene can be composed of which b2a2 and b3a2 are the most frequent. These fusion genes encode for a neo-protein, the BCR/ABL protein, which is unique to CML cells. Intracellular proteins are degraded by the proteasome into small peptides of 8 to 11 amino acids, which are subsequently bound to HLA class I in the endoplasmatic reticulum and transported to the cell membrane for presentation to T cells. Since CML-specific proteins contain amino acid sequences that are novel to the immune system, they might induce tumor-specific cytotoxic Tcell responses when presented by HLA molecules on leukemic cells. A prerequisite for such a response is proteasomal degradation of intracellular BCR/ABL protein resulting in presentation of BCR/ABL-specific oligopeptides by HLA class I or HLA class II molecules on the membrane of leukemic cells and the presence of T cells with a T-cell receptor (TCR) that can recognize these peptide-HLA complexes. Until now there is no definite proof of the existence of such CML-specific responses in vivo. Arguments in favor of the existence of CML-specific T-cell responses are the ability to generate immune responses in vitro against BCR/ABL-derived synthetic peptides presented by HLA class I or HLA class II molBackground and Objectives. Cytotoxic T-lymphocytes (CTL) have been generated in vitro against chronic myeloid leukemia (CML)-associated BCR/ABL-specific peptides. We analyzed the existence of high-avidity T cells recognizing endogenously processed BCR/ABL-specific proteins.