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

Author： Juffs Helen Fowler Nina Saal Russell Grimmett Karen Beasley Shannon O'Sullivan Brendan Frazer Ian gill Devinder Thomas Ranjeny

Publisher： Ashgate Publishing Ltd

ISSN： 0031-3025

Source： Pathology, Vol.36, Iss.1, 2004-02, pp. : 69-76

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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-γ 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-γ. Responsiveness of B-CLL MHC class I mRNA to IFN-γ 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 β₂m and β₂m-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.