pl50/95, Third member of the LFA‐1/CR3 polypeptide family identified by anti‐Leu M5 monoclonal antibody

Abstract

Monoclonal antibody (mAb) anti-Leu M5 reacts with a two-chain molecule composed of a 150-kDa α subunit noncovalently associated with a 95-kDa β subunit and probably is specific for an epitope on the 150-kDa β chain. This pl50/95 antigen is the third member of a family of polypeptides sharing a common 95-kDa β chain, which includes the lymphocyte function-associated antigen LFA-1 (p177/95) and complement receptor CR₃ (Mo1/MAC-1/OKM1; p165/95) antigens. Sequential immunoprecipitation with anti-p95 β chain mAb specifically removed the antigens detected by anti-LFA-1, anti-CR₃ and anti-Leu M5 mAb. Certain patients with recurrent bacterial infections are genetically deficient in expression of the LFA-1 and Mo1 antigens, and have impaired granulocyte function. Granulocytes from a patient with this disease also failed to react with anti-Leu M5. Stimulation of normal granulocytes with f-Met-Leu-Phe, C5a-desArg, or calcium ionophore resulted in increased expression of Mo1 and Leu M5 antigens on the cell surface, but did not significantly increase expression of LFA-1 antigen. In functional assays, anti-Leu M5 did not inhibit T cell-mediated or natural killer cell-mediated cytotoxicity. In addition, anti-Leu M5 neither inhibited the binding of complement-coated particles to CR₁ or CR₃ nor did it affect the binding of EC3dg to neutrophils (CR₄). These studies clearly indicate that the p150/95 antigen recognized by the anti-Leu M5 antibody is a structurally distinct member of the LFA- 1/CR₃ family.