SUPERANTIGEN-MEDIATED CELLULAR CYTOTOXICITY IS DEPENDENT ON ANTIGEN EXPRESSION, BUT INDEPENDENT OF THE P-GLYCOPROTEIN MULTIDRUG-RESISTANCE PHENOTYPE

Superantigen-activated T cells can be targeted by monoclonal antibodie s (mAb) to lyse MHC class II negative tumour cells. In this study we d etermined the susceptibility of the T-lymphoblastoid leukaemic cell li ne CCRF-CEM and its multidrug resistant sublines CCRF VCR100, CCRF VCR 1000 and CCRF ADR5000 to lysis by monoclonal antibody-targeted and sup erantigen-activated T cells (superantigen-dependent cellular cytotoxic ity, SDCC), A recombinant fusion protein of protein A and the superant igen Staphylococcus enterotoxin A (SEA) was used together with the mAb s anti-CD7, anti-CD38, anti-CD45RA and 4E3 (anti-P-glycoprotein) to co rrelate susceptibility to SDCC with expression of the MDR1-gene produc t, Our results demonstrated SDCC to be independent of MDR1-gene expres sion. This was further confirmed by blocking the function of Pgp in th e leukaemic cell lines with a cyclosporine A derivative, which had no influence on SDCC. As expected, expression of the respective cell surf ace antigens on target cells had a strong impact on SDCC, although oth er factors seem to influence efficiency of SDCC as well.