A monoclonal antibody (NKI-L16) directed against a unique epitope on the alpha-chain of human leukocyte function-associated antigen 1 induces homotypic cell-cell interactions.
In the present study a unique antibody (NKI-L16) reacting with the alpha-chain of the human leukocyte function-associated Ag-1 (LFA-1) is described, which stimulates homotypic cell-cell interactions in a manner very similar to 12-O-tetradecanoyl-phorbol-13-acetate (TPA), in contrast to other anti-LFA-1 mAb which inhibit cell aggregation. The induction of aggregate formation of EBV-transformed B cells (JY) and CTL clones by TPA or NKI-L16 is not accompanied by an increase in the expression of LFA-1. Nevertheless, this cluster formation is LFA-1 dependent, inasmuch as anti-LFA-1 antibodies, other than NKI-L16, completely abrogate aggregation. Simultaneous addition of NKI-L16 and TPA did not result in a further increase of the speed of cluster formation, suggesting that a similar pathway is activated. Immunoprecipitation and enzyme digestion studies revealed that NKI-L16 recognizes a unique epitope on the alpha-chain of LFA-1, most likely situated close to the transmembrane segment of the molecule. It is hypothesized that NKI-L16 or TPA can cause the LFA-1 molecule to convert from an inactive to an active configuration, thereby permitting binding of LFA-1 to its natural ligand.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology* / Q000302:isolation & purification; D002448:Cell Adhesion; D002449:Cell Aggregation; D002450:Cell Communication; D002460:Cell Line; D000939:Epitopes / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008807:Mice, Inbred BALB C; D011233:Precipitin Tests; D011961:Receptors, Fc / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D011961:Receptors, Fc