title: HLA-DR1-restricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen-presenting cells exposed to b3a2 containing cell lysates.
abstract: Chronic myeloid leukemia (CML) is characterized by a specific translocation of the c-abl oncogene on chromosome 9 to the break point cluster region (bcr) on chromosome 22, t(9;22) (q34;q11). This translocation results in the expression of a 210-kD bcr-abl protein fusion gene product. The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence, which may be presented by antigen-presenting cells and recognized specifically by human T lymphocytes. We have generated a CD4+ T lymphocyte line (NG-1) which recognizes the peptide epitope (GFKQSSKALQR) in association with HLA-DRbeta1*0101-02. A comparison of antigen-presenting cells showed that CMRF-44+ blood dendritic cell presented a 12mer b3a2 peptide effectively. The b3a2 peptide was able to generate specific primary T-lymphocyte responses in other HLA-DR1 donors. We also show that bcr-abl, b3a2 peptide-specific T-lymphocyte lines proliferate in response to bcr-abl b3a2 containing cell lysates (K562 or CML PBMC derived) but not control (including b2a2 CML PBMC) lysates.
authors.affiliation: Haematology/Immunology Research Group, Christchurch Hospital, New Zealand.
authors.forename: S I
authors.initials: SI
authors.lastname: Mannering
authors.forename: J L
authors.initials: JL
authors.lastname: McKenzie
authors.forename: D B
authors.initials: DB
authors.lastname: Fearnley
authors.forename: D N
authors.initials: DN
authors.lastname: Hart
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics; D015798:HLA-DR1 Antigen / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology
chemical_list: D015798:HLA-DR1 Antigen; D010455:Peptides; D016044:Fusion Proteins, bcr-abl