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 Ii(b2a2) construct

Peptides corresponding to the fusion site in 210 kD BCR-ABL protein b3a2 (p 210b3a2) were previously shown to bind to several HLA class I and II allele s. We have found that b3a2 peptide-specific CD4-positive T-helper cells wer e able to recognize p210b3a2-positive chronic myelogenous leukemia (CML) bl asts in a DR4 restricted manner. Until now, there were no reports of b2a2 b reakpoint-specific human T-cell responses. Here we show that repetitive sti mulation of T lymphocytes with a 17mer peptide covering the fusion region i n p210b2a2 also leads to specific T-cell responses. CD4 and CD4/CD8 double- positive clones obtained from a b2a2 peptide-specific cell line were cytoto xic and proliferative in an HLA-DR2a (DRB5*0101) restricted fashion. Autolo gous Epstein-Barr virus (EBV) transformed cells, expressing BCR-ABL(b2a2) o n transfection, and allogeneic HLA-DR matched p216b2a2-positive cells from CML patients were, however, not lysed. BCR-ABL peptide-specific T-cell clon es 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, illustratin g the potential of these T cells to recognize an endogenous BCR-ABL(b2a2) l igand. (C) 1999 by The American Society of Hematology.