Synthetic peptides derived from the Wilms' tumor 1 protein sensitize human T lymphocytes to recognize chronic myelogenous leukemia cells.
The Wilms' tumour 1 (WT1) molecule was screened in silico for the presence of 15-mer sequences predicted to bind HLA-DRB1(*)0401 (www.syfpeithi.de). Two peptides with the highest binding scores were synthesized (WT12e, PQQMGSDVRDLNALL and WT331, NKRYFKLSHLQMHSR). In vitro sensitization experiments using PBMC and the 15-mer peptides yielded peptide-specific responses against both WT12e and WT331 from six of seven healthy donors. Moreover, four of four different primary CML cell preparations were directly recognized by five different T cell lines, as assessed by IFN-gamma release. These responses were to a great extent blocked by anti-DR monoclonal antibody. These results suggest that WT1 peptides can be selected that are immunogenic for class II-restricted T-cell responses to native tumor cells, and indicate that they may find application in active immunotherapy of CML.
Müller
Ludmila
L
Tübingen Ageing and Tumor Immunology Group, Second Department of Internal Medicine, University of Tübingen Medical School, Germany. ludmila.mueller@med.uni-tuebingen.de
Knights
Ashley
A
Pawelec
Graham
G
D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D019898:Autocrine Communication / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D025721:WT1 Proteins / Q000737:chemistry* / Q000276:immunology / Q000502:physiology
D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D010446:Peptide Fragments; D025721:WT1 Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor