BCR/ABL leukemia oncogene fusion peptides selectively bind to certain HLA-DR alleles and can be recognized by T cells found at low frequency in the repertoire of normal donors

摘要: Chronic myelogenous leukemia (CML) is characterized by the t(9;22) translocation that results in chimeric genes encoding bcr/abl fusion proteins. Junction-spanning sequences represent unique tumor-specific moieties might be exploited therapeutically. We investigate here binding of synthetic peptides to various HLA-DR alleles and their recognition T cells from normal donors CML patients. A 23- mer b3/a2 peptide bound very strongly isolated HLA-DRB1*1101 (Dw5) relatively DRB1*0301 (Dw3) DRB1*0402 (Dw10) molecules, as estimated using a competition assay. It failed bind several other DR alleles, including three different DR4 alleles. In contrast, 23-mer b2/a2 only allele. Peripheral blood mononuclear were sensitized vitro against peptide. After four repetitive stimulations, responding found at low frequency 5 11 tested. Three five HLA- DR11+, all DR11+ tested respond. recognizing not identified any patients studied, regardless HLA type. Finally, even peptide- reactive T-cell lines stimulated native absence exogenous These show presence low-frequency major histocompatability complex class II- restricted bcr/abl-responses repertoire with certain types, but suggest unmodified tumor cannot recognized such peptide-sensitized cells.