title: A novel MHC-associated proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias.
abstract: Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the overexpressed proteins WT1 and Proteinase 3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/Abl transformation were also identified. Our investigation is the second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients', these data further support the application of this antigen as an immunotherapeutical target for myelogenous leukaemias.
authors.affiliation: Section for Transplantation Immunology and Immunohaematology, University Hospital Tübingen, ZMF, Waldhörnlestrasse 22, Tübingen, Germany. ashley.knights@usz.ch
authors.forename: A J
authors.initials: AJ
authors.lastname: Knights
authors.forename: A O
authors.initials: AO
authors.lastname: Weinzierl
authors.forename: T
authors.initials: T
authors.lastname: Flad
authors.forename: B-A
authors.initials: BA
authors.lastname: Guinn
authors.forename: L
authors.initials: L
authors.lastname: Mueller
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: S
authors.initials: S
authors.lastname: Stevanovic
authors.forename: G
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000939:Epitopes / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy; D008024:Ligands; D053146:Myeloblastin; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D012697:Serine Endopeptidases / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012697:Serine Endopeptidases; D053146:Myeloblastin