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

Authors: Helen Juffs a;  Nina Fowler a;  Russell Saal b;  Karen Grimmett b;  Shannon Beasley a;  Brendan O'Sullivan a;  Ian Frazer a;  Devinder gill b; Ranjeny Thomas a
Affiliations:   a Centre for Immunology and Cancer Research, University of Queensland, Qld
b Division of Haematology, Princess Alexandra Hospital, Brisbane, Qld, Australia
DOI: 10.1080/00313020310001644499
Publication Frequency: 7 issues per year
Published in: journal Pathology, Volume 36, Issue 1 February 2004 , pages 69 - 76
Subject: Pathology;
Number of References: 38
Formats available: PDF (English)
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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.
Keywords: Human; B-CLL; antigen presentation; MHC class I; TAP
view references (38)
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