Regulation and Functional Involvement of Distinct Determinants of Leucocyte Function‐Associated Antigen 1 (LFA‐1) in T‐Cell Activation In Vitro

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Abstract
The expression of leucocyte function‐associated antigen 1 (LFA‐1) was studied by immunofluorescence method on human peripheral blood mononuclear cells (PBMC) stimulated by the phytohaemagglutinin lectin (PHA).Monoclonal antibodies (MoAb) Mas 191c. IOT18 (directed against the β‐chain. 95 kDa. CDI8) and IOT16. SPVL7, MHM24 (identificating the α‐chain. 180 kDa, CD11a) were used, defining the CD 11a/ CD18' antibody panel.By means of cross‐linking or competitive experiments, we showed that these antibodies recognized al least four distinct and spatially distant domains on the LFA‐t molecule.Immunofluorescence analysis revealed that the up‐regulation of LFA‐1 expression was a late event, similar to the expression kinetics of the HLA DR and CD38 molecules, and followed the appearance of 0025 and CD71 molecules. Moreover, it was established that the LFA‐1 up‐regulation required mRNA and protein synthesis.Functional activity comparison of the different anti LFA‐1 MoAb showed that the CDI la MoAb significantly inhibited the proliferation of lymphocytes stimulated by the phytohaemagglutinin lo various extents, as the LFA‐ 1α determinant identified, By contrast, the CD 18 MoAb did not influence strongly this cell process. We observed only n dim inhibitory effect with the CD18 MoAb recognizing an epitope common or very close to an LFA‐1 α determinant.These results suggested that the LFA‐1 antigen was important, at a molecular level, in the regulation of T‐cell activation.