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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1038-1045
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
George J.A. ten Bosch,
Jan H. Kessler,
Antonia M. Joosten,
Alexandra A. Bres-Vloemans,
Annemieke Geluk,
Barbara C. Godthelp,
Jeroen van Bergen,
Cornelis J.M. Melief, and
Onno C. Leeksma
From the Department of Immunohematology and Bloodbank, Leiden
University Medical Center, Leiden, The Netherlands.
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-ABLb2a2 ligand.

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