Effects of Ly-5 antibodies on antibody-dependent cell-mediated cytotoxicity (ADCC)

Antibodies to a number of cell surface antigens expressed on mouse spleen cells were tested for their ability to inhibit antibody-dependent cell-mediated cytotoxicity (ADCC) of antibody-coated sheep erythrocytes (Ab-SE) in the absence of complement. Of the antibodies tested, only the antisera to Ly-5 and H-2 antigens significantly inhibited ADCC by spleen cells reactive with those antisera. Inhibition by Ly-5 antisera was shown to be allotype-specific by inhibition experiments using C57BL/6-Ly-5.1 (B6-Ly-5.1) and congenic C57BL/6-Ly-5.2 (B6-Ly-5.2) mice. Inhibition by Ly-5.1 antiserum appeared not to be due to competition for the Fc receptor (FcR), since in mixing experiments 'third-party' thymus cells treated with Ly-5 antiserum did not inhibit the cytotoxic activity of untreated cells. In comparing inhibition induced by antisera to H-2 and Ly-5 antigens, Ly-5.1 antiserum was more inhibitory at nearly every dilution tested. In addition, F(ab')2 fragments of Protein A-purified Ly-5.1 antibody were inhibitory to BALB/c spleen effector cells in ADCC of Ab-SE, whereas F(ab')2 fragments of H-2 antibodies had no effect. Because ADCC of tumour cells may share a common lytic mechanism with ADCC of erythrocytes, several antisera to cell surface antigens found on spleen cells were tested for inhibition of ADCC to antibody-coated P815 tumour cells (Ab-P815). As seen in ADCC to Ab-SE, anti-Ly-5.1 was a more potent inhibitor than antibody against either H-2k or H-2d antigens. The results are discussed in the light of the ability of Ly-5 antisera to inhibit various types of cell-mediated killing.