Recognition of peptides corresponding to the joining region of p210BCR-ABL protein by human T cells.
In chronic myeloid leukemia (CML) the proto-oncogene c-abl from chromosome 9 q34 is translocated to the breakpoint cluster region (bcr) gene on chromosome 22 q11. This translocation results in a BCR-ABL fusion gene, which encodes chimeric fusion oncoproteins p210BCR-ABL. Here we demonstrate that a peptide with joining region sequence ATGFKQSSKALQRPVAS (eight amino acids (aa) encoded by BCR exon 3; one novel lysine, encoded by the fusion codon; eight aa encoded by ABL exon 2) is immunogenic to human T cells. Primary immune response induction with this peptide resulted in a HLA DR2(DRB1*1501) restricted CD4+ BCR-ABL peptide specific T cell line P1. Responses of P1 were negatively affected by individual aa replacement by alanine at eight aa positions within the 17mer peptide (F4, K5, Q6, K9, L11, Q12, R13, P14). These findings were supported by experiments with a panel of overlapping 11mer b3a2 peptides. Only two of these peptides with an aa sequence encompassing all residues which could not be replaced by alanine induced P1 proliferation. Since presentation of cytosolic oncoproteins as peptides by DR molecules has been observed, the present findings provide a possible explanation for post interferon-alpha persisting remissions in spite of the presence of BCR-ABL PCR positive progenitors.
ten Bosch
G J
GJ
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Toornvliet
A C
AC
Friede
T
T
Melief
C J
CJ
Leeksma
O C
OC
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D018604:Epitope Mapping; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D000090063:Proto-Oncogene Mas; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D006684:HLA-DR Antigens; C000715470:MAS1 protein, human; D010455:Peptides; D000090063:Proto-Oncogene Mas; D016044:Fusion Proteins, bcr-abl