Is the T-cell receptor involved in T-cell killing?

Abstract

It is known that when two populations of cytotoxic T lymphocytes (CTL) are mixed in conditions where antigen recognition can occur in only one direction, killing also proceeds only in the same direction^1,2. These data suggest that occupancy of the T-cell receptor (TCR) is required for the expression of the lytic function by effector CTL, but do not establish whether the TCR itself has a role in the killing process. In particular, it is not clear whether the TCR is involved in the actual delivery of the lethal hit to the target cell (either being itself part of the lytic machinery or directing it), or whether TCR occupancy only serves the function of triggering a set of lytic reactions which are themselves nonspecific and not directed by the TCR. The use of mitogenic lectins or mitogenic antibodies, which bypass specific recognition and induce nonspecific killing^3–5, also does not help to clarify this issue, since a necessary characteristic of these ligands is that they bind to the TCR complex or to other ‘triggering’ molecules and probably bridge these structures to the target cell^6,7. The present study describes an in vitro system using human T-cell clones which allows us to dissociate the triggering of a CTL from the delivery of the lethal hit, using no externally added ligands. We report that, once triggered by recognition of the specific target, a CTL can kill any other cell that binds to it, indicating that TCR occupancy is required for triggering, but not for the delivery of the lethal hit.