B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma

Pathology. 2004 Feb;36(1):69-76. doi: 10.1080/00313020310001644499.

Abstract

Aims: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / immunology
  • Aged
  • Antigen Presentation / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / drug effects
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Polymerase Chain Reaction

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Histocompatibility Antigens Class I
  • TAP1 protein, human
  • TAP2 protein, human
  • Interferon-gamma