The in vitro generation of Ph1+ ALL-specific HLA-A24-restricted cytotoxic T lymphocytes using a synthetic 16 mer minor bcr-abl peptide.
Sixteen mer peptide, which spans the junctional region of the acute lymphoid leukemia (ALL)-specific minor bcr-abl fusion protein and contains a motif that can bind to human leukocyte antigen (HLA)-A24, was constructed. We tried to generate Philadelphia chromosome 1 (Ph1) positive ALL-specific cytotoxic T lymphocytes (CTLs) from eight normal HLA-A24+ individuals with peptide-pulsed autologous dendritic cells (DCs). CTLs could be generated from the mononuclear cells (MNCs) of a single donor, which could kill peptide-pulsed autologous DCs and two A24+ ALL lines, while an HLA-A24+ CML line was only weakly killed and unpulsed DCs or the control lines Daudi or K562 were not recognized. Those CTLs consisted predominantly of CD8+ T cells whose cytotoxicity could be neutralized by monoclonal antibodies to HLA-class I or HLA-A24, and also produced interferon (IFN)-gamma after being stimulated with peptide-pulsed DCs.
Hagihara
Masao
M
Department of Hematology and Rheumatology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. masaoha@is.icc.u-tokai.ac.jp
Tsuchiya
Takahide
T
Hyodo
Osamu
O
Ueda
Yoko
Y
Tazume
Kei
K
Gansuvd
Balgansuren
B
Kato
Shunichi
S
Hotta
Tomomitsu
T
D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D009842:Oligopeptides; D007371:Interferon-gamma; D016044:Fusion Proteins, bcr-abl