Fas was initially described as a molecule expressed on the surface of
certain cell lines that could mediate programmed cell death (apoptosis
) subsequent to ligation by specific mAb. To determine whether mAb to
other epitopes on the Fas molecule might mediate other functions, we g
enerated a panel of mAb to the extracellular portion of human Fas. Sig
nificant lysis of Fas-expressing target cells was only observed when t
he new mAb were first bound to a solid-phase support and not when the
mAb were added in solution. However, several of these mAb inhibited th
e killing of target cells induced by the prototypic Fas-specific mAb,
CH-11. Those mAb that inhibited apoptosis of target cells mediated by
the CH-11 mAb also blocked lysis of target cells mediated by cells exp
ressing Fas ligand. Finally, some of the Fas-specific mAb were found t
o co-stimulate proliferation of peripheral blood T cells in the presen
ce of immobilized CD3 mAb. Thus, the data indicate the existence of a
complex set of interactions mediated by Fas in both normal and transfo
rmed lymphoid cells that may have important implications regarding the
role(s) of this molecule in regulation of immune responses.