A BCR-ABL Oncoprotein p210b2a2 Fusion Region Sequence Is Recognized by HLA-DR2a Restricted Cytotoxic T Lymphocytes and Presented by HLA-DR Matched Cells Transfected With an Iib2a2 Construct

• Published in: Blood Vol. 94; no. 3; pp. 1038 - 1045
• Main Authors: ten Bosch, George J.A., Kessler, Jan H., Joosten, Antonia M., Bres-Vloemans, Alexandra A., Geluk, Annemieke, Godthelp, Barbara C., van Bergen, Jeroen, Melief, Cornelis J.M., Leeksma, Onno C.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.08.1999; The Americain Society of Hematology
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Human; Breakpoint; Immune response; Peptides; HLA-DR-System; Cytotoxicity; Malignant hemopathy; Cellular immunity; In vitro; Myeloproliferative syndrome; Chronic; Histocompatibility restriction; Immunological investigation; C-Onc gene; Chronic myelocytic leukemia; T-Lymphocyte; Cytogenetics; Genetics; Fusion protein; Tumor cell; Hybrid gene; Protooncogene
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V94.3.1038.415k22_1038_1045

Peptides corresponding to the fusion site in 210 kD BCR-ABL protein b3a2 (p210b3a2) were previously shown to bind to several HLA class I and II alleles. We have found that b3a2 peptide-specific CD4-positive T-helper cells were able to recognize p210b3a2-positive chronic myelogenous leukemia (CML) blasts in a DR4 restricted manner. Until now, there were no reports of b2a2 breakpoint-specific human T-cell responses. Here we show that repetitive stimulation of T lymphocytes with a 17mer peptide covering the fusion region in p210b2a2 also leads to specific T-cell responses. CD4 and CD4/CD8 double-positive clones obtained from a b2a2 peptide-specific cell line were cytotoxic and proliferative in an HLA-DR2a (DRB5*0101) restricted fashion. Autologous Epstein-Barr virus (EBV) transformed cells, expressing BCR-ABLb2a2 on transfection, and allogeneic HLA-DR matched p210b2a2-positive cells from CML patients were, however, not lysed. BCR-ABL peptide-specific T-cell clones did respond to autologous EBV cells transfected with invariant chain (li) cDNA in which the HLA class II–associated invariant chain peptide (CLIP) was replaced by a BCR-ABL b2a2 fusion oligonucleotide sequence, illustrating the potential of these T cells to recognize an endogenous BCR-ABLb2a2ligand.