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Superantigen‐mediated cellular cytotoxicity is dependent on antigen expression, but independent of the P‐glycoprotein multidrug resistance phenotype
Author(s) -
Zehrer Cornelia,
Beck James,
Gekeler Volker,
Ihle Johannes,
Holzer Ursula,
Dohlsten Mikael,
Kalland Terje,
Niethammer Dietrich,
Dannecker GU¨nther E.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1938.x
Subject(s) - superantigen , antigen , monoclonal antibody , biology , cytotoxicity , microbiology and biotechnology , t cell , antibody , immunology , in vitro , immune system , biochemistry
Superantigen‐activated T cells can be targeted by monoclonal antibodies (mAb) to lyse MHC class II negative tumour cells. In this study we determined the susceptibility of the T‐lymphoblastoid leukaemic cell line CCRF‐CEM and its multidrug resistant sublines CCRF VCR100, CCRF VCR1000 and CCRF ADR5000 to lysis by monoclonal antibody‐targeted and superantigen‐activated T cells (superantigen‐dependent cellular cytotoxicity, SDCC). A recombinant fusion protein of protein A and the superantigen Staphylococcus enterotoxin A (SEA) was used together with the mAbs anti‐CD7, anti‐CD38, anti‐CD45RA and 4E3 (anti‐P‐glycoprotein) to correlate susceptibility to SDCC with expression of the MDR1‐gene product. Our results demonstrated SDCC to be independent of MDR1‐gene expression. This was further confirmed by blocking the function of Pgp in the leukaemic cell lines with a cyclosporine A derivative, which had no influence on SDCC. As expected, expression of the respective cell surface antigens on target cells had a strong impact on SDCC, although other factors seem to influence efficiency of SDCC as well.