title: Immunological characterization of the tumor-specific bcr/abl junction of Philadelphia chromosome positive chronic myeloid leukemia.
abstract: Recent developments in the understanding of the process of antigen presentation by major histocompatibility complex (MHC) molecules and their recognition by T-lymphocytes has led investigators to speculate that the hybrid bcr/abl fusion protein P210 present in chronic myeloid leukemia (CML) cells may generate leukemia-specific antigens recognized by T-cells. We used synthetic peptides representing the fusion region of P210 to study MHC class I and class II pathways of antigen recognition in normal subjects and patients with CML. We found that most normal individuals have a low proliferative response to 18mer fusion peptides representing the two alternative splicing variants b2a2 and b3a2, and a T-lymphocyte precursor frequency (HTLPf) characteristic of unprimed responders. No increase in HTLPf was found in CML patients after bone marrow transplantation (BMT), suggesting that peptide recognition does not form part of the graft-versus-leukemia process. In contrast, untransplanted patients with CML had very high HTLPf, suggesting an autologous but immunologically ineffective recognition of leukemia-specific peptides through HLA class II. Preliminary studies using the T2 cell line (which expresses HLA class I only in the presence of peptides binding to HLA-A2) indicate that nonapeptides spanning the breakpoint of the b2a2 and b3a2 variants of P210 do not bind to this particular class I molecule and are therefore unlikely to initiate class I mediated lymphocyte responses.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Barrett
authors.forename: A
authors.initials: A
authors.lastname: Guimaraes
authors.forename: J
authors.initials: J
authors.lastname: Cullis
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D010455:Peptides / Q000737:chemistry; D013234:Stem Cells / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000473:pathology
chemical_list: D015789:HLA-A2 Antigen; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C075525:A2-binding peptide; D016044:Fusion Proteins, bcr-abl