G. Gorochov et al., ANTILEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 ANTIBODIES INHIBIT T-CELLACTIVATION FOLLOWING LOW-AVIDITY AND ADHESION-INDEPENDENT INTERACTIONS, Immunology, 79(4), 1993, pp. 548-555
Anti-leucocyte function-associated antigen-1 (LFA-1) antibodies can pr
ovide either stimulatory or inhibitory signals to T cells, depending o
n the epitope they recognize, type and stage of activation of the T ce
lls, and nature of the activation stimulus. Because of the low affinit
y of interaction between the T-cell receptor (TcR) and the antigen/maj
or histocompatibility complex (MHC), it was proposed that the LFA-1 mo
lecule strengthens the adhesion between the interacting cells, thus co
ntributing in an additive manner to TcR-specific interactions. To chec
k if high-avidity, TcR-specific interactions still require the accesso
ry function of the adhesion molecule, we studied the effect of anti-LF
A-1 antibodies on T-cell triggering mediated through chimeric receptor
s composed of an Fv of an antibody and a constant region of the TcR. S
uch chimeric TcR (cTcR) confer on T cells antibody-type specificity an
d affinity. We made use of transfected T-cell hybridomas expressing va
rious amounts of either one cTcR chain (composed of V(H) linked to Cbe
ta) or double-chain cTcR (V(H)C(beta)+V(L)Calpha). When such transfect
ants were stimulated with hapten-modified cells, anti-LFA-1 antibodies
inhibited activation predominantly mediated through cTcR composed of
a single chimeric chain and did not inhibit stimulation of the double-
chain transfectants. Moreover, these anti-LFA-1 antibodies blocked ant
igen-specific T-cell activation regardless of whether the stimulus was
adhesion dependent or not, such as in the case of stimulation by immo
bilized hapten-protein conjugates. These studies show that the 'off-si
gnal' provided by anti-LFA-1 antibodies is adhesion independent and af
fects mainly low-avidity TcR-antigen interactions.