b3a2 BCR-ABL fusion peptides as targets for cytotoxic T cells in chronic myeloid leukaemia.
Peptide sequences spanning the BCR-ABL protein junction potentially constitute novel leukaemia-specific antigens. 9-mer b3a2 fusion peptides have been reported to bind with high affinity to HLA-A3, -A11 and -B8. We have studied the effect of b3a2 BCR-ABL junctional peptides on the cytotoxic T-cell (CTL) response against normal and chronic myeloid leukaemia (CML) cells. Antigen-presenting cells (APCs) were prepared from HLA-A3- or -B8-positive peripheral blood mononuclear cells (PBMCs) by incubation with phytohaemagglutinin (PHA) and interleukin (IL)-2 for 7 d. These APCs were pulsed with the respective b3a2 junctional peptide in the presence of beta2-microglobulin and were then used to challenge autologous PBMCs at 7-d intervals in the presence of IL-2, IL-6, IL-7 and IL-12. On subsequent exposure to target cells (either further pulsed normal APCs or unpulsed CML cells), specific HLA-restricted CTL responses were observed against all HLA-A3/-B8 matched normal target cells tested, but not to targets that were HLA mismatched. Cytotoxicity was also induced against HLA-A3/-B8 unpulsed CML cells, but not against unmatched CML cells. These data indicate (i) that endogenous BCR-ABL junctional peptides may be presented by CML cells and (ii) that exogenous peptides are potential stimulators of autologous antileukaemic CTLs.
Norbury
L C
LC
University Departments of Haematology and Immunology, Royal Liverpool University Hospital, UK.
Clark
R E
RE
Christmas
S E
SE
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D015791:HLA-A3 Antigen; D015795:HLA-B8 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015791:HLA-A3 Antigen; D015795:HLA-B8 Antigen; D007376:Interleukin-2; D015850:Interleukin-6; D015851:Interleukin-7; D018664:Interleukin-12; D016044:Fusion Proteins, bcr-abl