Role of CD8 in staphylococcal enterotoxin B-mediated lysis by cytotoxic T lymphocytes

Recent evidence has suggested that recognition of superantigens such as the staphylococcal enterotoxins by CTL occurs independently of the accessory molecule CD8. These conclusions are based on the observation that antibodies to CD8 do not appear to be effective inhibitors of T cell lysis that is mediated by enterotoxin. This is in contrast to the well-known inhibitory effects of anti-CD8 antibodies on T cell activation by most peptide/class I complexes. In this study, we show that lysis of staphylococcus enterotoxin B (SEB)-bearing target cells by the mouse alloreactive CTL clone 2C is inhibited by anti-CD8 antibodies. SEB-mediated lysis by a polyclonal population of mouse CTL was also inhibited by anti-CD8 antibodies, but only under conditions where the SEB concentration is low. Inhibition occurs even when class I negative Daudi cells are used as targets. Thus, the observed inhibition does not appear to be due to the prevention of intercellular interactions between CD8 and class I molecules but is probably a consequence of preventing the intracellular association of CD8 and TCR. At the high ligand densities used in most previous studies, very few of the CD8/TCR complexes may be required for activation. Under these conditions, lysis may appear to be CD8 "independent" because 1) there are a sufficient number of preexisting CD8/TCR complexes for activation; or 2) prohibitively high concentrations of antibody would be needed to saturate unassociated CD8.