title: B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma.
abstract: OBJECTIVE
  An important consideration in the design of a tumour vaccine is the ability of tumour-specific cytotoxic T lymphocytes (CTL) to recognise unmanipulated tumour cells in vivo. To determine whether B-CLL might use an escape strategy, the current studies compared B-CLL and normal B cell MHC class I expression.
  
  
  METHODS
  Flow cytometry, TAP allele PCR and MHC class I PCR were used.
  
  
  RESULTS
  While baseline expression of MHC class I did not differ, upregulation of MHC class I expression by B-CLL cells in response to IFN-gamma was reduced. No deletions or mutations of TAP 1 or 2 genes were detected. B-CLL cells upregulated TAP protein expression in response to IFN-gamma. Responsiveness of B-CLL MHC class I mRNA to IFN-gamma was not impaired.
  
  
  CONCLUSIONS
  The data suggest that MHC class I molecules might be less stable at the cell surface in B-CLL than normal B cells, as a result of the described release of beta(2)m and beta(2)m-free class I heavy chains from the membrane. This relative MHC class I expression defect of B-CLL cells may reduce their susceptibility to CTL lysis in response to immunotherapeutic approaches.
authors.affiliation: Centre for Immunology and Cancer Research, University of Queensland, Brisbane, Qld., Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Juffs
authors.forename: Nina
authors.initials: N
authors.lastname: Fowler
authors.forename: Russell
authors.initials: R
authors.lastname: Saal
authors.forename: Karen
authors.initials: K
authors.lastname: Grimmett
authors.forename: Shannon
authors.initials: S
authors.lastname: Beasley
authors.forename: Brendan
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Ian
authors.initials: I
authors.lastname: Frazer
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000276:immunology; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D007371:Interferon-gamma