Is CD8 dependence a true reflection of TCR affinity for antigen?

Cytotoxic T lymphocytes (CTL) are generally specific for class I MHC proteins plus antigen and express CD8 co-receptor molecules. The effector function of some CTL can be blocked by antibodies to CD8 (CD8 dependent CTL), whereas that of others is resistant to blocking (CD8 independent CTL). This difference in sensitivity to antibody-mediated inhibition is assumed to reflect variations in affinity of particular TCR for antigen. However, we have found that a major difference between CD8 independent and CD8 dependent T cells lies in their sensitivity to stimulation, the former responding to lower concentrations of anti-CD3 antibody than the latter. Thus the contribution to cell signalling provided by the co-association of p56lck and CD8 is particularly relevant for CD8 dependent cells. These data challenge the notion that the affinity of an individual TCR for antigen is related to the sensitivity of a cell to inhibition by anti-CD8 antibodies. Furthermore we show that antibodies to co-receptor molecules have multiple distinct effects on T cell activation, only some of which may be related to T cell affinity.