The in vitro generation of Ph1+ ALL-specific HLA-A24-restricted cytotoxic T lymphocytes using a synthetic 16 mer minor bcr–abl peptide

Abstract 

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)-γ after being stimulated with peptide-pulsed DCs.

Abbreviations:  ALL, acute lymphoid leukemia, HLA, human leukocyte antigen, Ph1, Philadelphia chromosome 1, MNCs, mononuclear cells, CML, chronic myeloid leukemia, DCs, dendritic cells, IFN, interferon, IL, interleukin, CTLs, cytotoxic T lymphocytes, DLI, donor T lymphocyte infusion, LPS, lipopolysaccharide, TNF, tumor necrosis factor, GM-CSF, granulocyte–macrophage colony stimulating factor, LAKs, lymphokine-activated killers, mAb, monoclonal antibodies

Keywords:  Ph1-ALL, HLA-A24, Peptide, Dendritic cell, Cytotoxic T lymphocytes