ANTILEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 ANTIBODIES INHIBIT T-CELLACTIVATION FOLLOWING LOW-AVIDITY AND ADHESION-INDEPENDENT INTERACTIONS

Citation
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
Citations number
30
Categorie Soggetti
Immunology
Journal title
ISSN journal
00192805
Volume
79
Issue
4
Year of publication
1993
Pages
548 - 555
Database
ISI
SICI code
0019-2805(1993)79:4<548:AFAAIT>2.0.ZU;2-9
Abstract
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.