Cytotoxic T lymphocytes (CTL) are generally specific for class I MHC p
roteins plus antigen and express CD8 co-receptor molecules. The effect
or function of some CTL can be blocked by antibodies to CD8 (CD8 depen
dent CTL), whereas that of others is resistant to blocking (CD8 indepe
ndent CTL). This difference in sensitivity to antibody-mediated inhibi
tion is assumed to reflect variations in affinity of particular TCR fo
r antigen. However, we have found that a major difference between CD8
independent and CD8 dependent T cells lies in their sensitivity to sti
mulation, the former responding to lower concentrations of anti-CD3 an
tibody than the latter. Thus the contribution to cell signalling provi
ded by the co-association of p56lck and CD8 is particularly relevant f
or CD8 dependent cells. These data challenge the notion that the affin
ity 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 affinit
y.