Effects of monoclonal antibodies to the a and β chains of the human lymphocyte function‐associated (H‐LFA‐1) antigen on T lymphocyte functions

AbstractThe ability of two antibodies, one specific for the a chain, p180, and the other for the β chain, p95, of the human lymphocyte function‐associated (LFA‐1) antigens, to inhibit T cell function was measured. Both antibodies inhibited T cell‐mediated lysis of virus‐infected target cells and of K562 cells. Only the anti‐β chain antibody inhibited natural killer cell lysis of K562. The antibodies inhibited cytotoxic T lymphocyte cell (CTL) lysis of HLA‐mismatched target cells in the presence of concanavalin A at 6.25–12.5 μg/ml, but at higher doses of Con A no inhibition was seen. When the lytic process was divided into calcium‐independent (adherence) and ‐dependent (lysis) steps the antibodies were found to block at the initial step of conjugate formation. The effects of these antibodies on T cell proliferative responses showed that responses to antigens, alloantigens, mitogens and anti‐CD3 (UCHT1) antibody were greatly inhibited. All of these responses are adherent cell dependent and proliferation of adherent cell‐depleted mononuclear cells to Sepharose‐coupled UCHT1 was not inhibited by anti‐LFA‐1 antibodies. Proliferation to paired anti‐CD2 (T11) antibodies was also only weakly inhibited. Release of interferon‐γ by CTL on contact with target cells was also inhibited by anti‐LFA antibody. These results are evidence that the LFA antigen is necessary for a nonspecific interaction with antigen ‐presenting cells that is essential for activation of T cells through the CD3‐T cell receptor complex.