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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
G Pawelec, H Max, T Halder, O Bruserud, A Merl, P da Silva and H Kalbacher
Second Department of Internal Medicine, Tubingen University Medical School,
Germany.
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 that might be exploited therapeutically. We investigate here the
binding of synthetic bcr/abl peptides to various HLA-DR alleles and their
recognition by T cells from normal donors and CML patients. A 23- mer b3/a2
peptide bound very strongly to isolated HLA-DRB1*1101 (Dw5) and relatively
strongly to DRB1*0301 (Dw3) and DRB1*0402 (Dw10) molecules, as estimated
using a competition assay. It failed to bind to several other DR alleles,
including three different DR4 alleles. In contrast, a 23-mer b2/a2 peptide
bound only to the DRB1*0301 (Dw3) allele. Peripheral blood mononuclear
cells from normal donors were sensitized in vitro against the b3/a2
peptide. After four repetitive stimulations, T cells responding to the
peptide were found at low frequency in 5 of the 11 donors tested. Three of
the five were HLA- DR11+, and all three of the DR11+ donors tested were
found to respond. T cells recognizing bcr/abl peptides were not identified
in any of the CML patients studied, regardless of HLA type. Finally, even
peptide- reactive T-cell lines from normal donors were not stimulated by
native CML cells in the absence of exogenous peptide. These results show
the presence of low-frequency major histocompatability complex class II-
restricted bcr/abl-responses in the normal T-cell repertoire of donors with
certain HLA types, but suggest that unmodified tumor cells cannot be
recognized by such peptide-sensitized T cells.
Volume 88,
Issue 6,
pp. 2118-2124,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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