title: Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL.
abstract: Using the allo-restricted T-cell approach to circumvent tolerance, we have previously identified a cytotoxic T-lymphocyte (CTL) epitope in the transcription factor Wilms tumor antigen 1 (WT1) presented by HLA-A0201 (A2) class I molecules. Here we describe an additional A2-presented epitope and show that CTLs against both epitopes kill WT1-expressing leukemia cell lines. Colony-forming assays demonstrated that both types of CTL killed CD34(+) progenitor cells from A2(+) leukemia patients, but not from A2(+) healthy individuals. The long-term culture-initiating cell (LTC-IC) assay was used to analyze the killing activity of WT1-specific CTLs against the more immature fraction of CD34(+) cells. The CTLs killed LTC-ICs of patients with chronic myelogenous leukemia (CML), whereas the function of normal CD34(+) progenitor/stem cells was not inhibited. Together, the data show that CTLs specific for 2 distinct peptide epitopes of WT1 can discriminate between normal and leukemia LTC-ICs, suggesting that such CTLs have the potential to selectively kill CML progenitor/stem cells.
authors.affiliation: Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bellantuono
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.forename: Suzanne
authors.initials: S
authors.lastname: Parry
authors.forename: Steve
authors.initials: S
authors.lastname: Marley
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.forename: Jane
authors.initials: J
authors.lastname: Apperley
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Stauss
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007519:Isoantigens; D025721:WT1 Proteins