title: Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein.
abstract: The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leukemia (CML). Here, tandem nanospray mass spectrometry was used to demonstrate cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR on class I-negative CML cells transfected with HLA-A*0301, and on primary CML cells from HLA-A3-positive patients. These patients mounted a cytotoxic T-lymphocyte response to KQSSKALQR that also killed autologous CML cells, and tetramer staining demonstrated the presence of circulating KQSSKALQR-specific T cells. The findings are the first demonstration that CML cells express HLA-associated leukemia-specific immunogenic peptides and provide a sound basis for immunization studies against BCR-ABL.
authors.affiliation: Department of Life Sciences and Chemistry and Physics, Nottingham Trent University, Nottingham, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: I A
authors.initials: IA
authors.lastname: Dodi
authors.forename: S C
authors.initials: SC
authors.lastname: Hill
authors.forename: J R
authors.initials: JR
authors.lastname: Lill
authors.forename: G
authors.initials: G
authors.lastname: Aubert
authors.forename: A R
authors.initials: AR
authors.lastname: Macintyre
authors.forename: J
authors.initials: J
authors.lastname: Rojas
authors.forename: A
authors.initials: A
authors.lastname: Bourdon
authors.forename: P L
authors.initials: PL
authors.lastname: Bonner
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: S E
authors.initials: SE
authors.lastname: Christmas
authors.forename: P J
authors.initials: PJ
authors.lastname: Travers
authors.forename: C S
authors.initials: CS
authors.lastname: Creaser
authors.forename: R C
authors.initials: RC
authors.lastname: Rees
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020014:K562 Cells / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015791:HLA-A3 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl