Structural homology of a macrophage differentiation antigen and an antigen involved in T-cell-mediated killing

Abstract

Two distinct murine cell-surface differentiation antigens, Mac-1 and LFA-1 (lymphocyte function-associated antigen 1), are compared here and shown to be related at the molecular level. Mac-1, defined by the M1/70 rat anti-mouse monoclonal antibody (MAb), is expressed on macrophages, natural killer cells and 50% of bone marrow cells, but not on B or T lymphocytes^1–3. In contrast, the LFA-1 antigen, defined by the M7/14 rat anti-mouse MAb, is expressed on B and T lymphocytes and 75% of bone marrow cells, but not on thioglycollate-induced peritoneal exudate macrophages^4,5. MAb blocking studies suggest that LFA-1 participates in T-lymphocyte-mediated killing and T-lymphocyte antigen-specific responses^4,5. Mac-1 and LFA-1 have α-polypeptide chains of 170,000 and 180,000 molecular weight (M_r), respectively, and both contain β polypeptides of 95,000 M_r. This similarity prompted us to investigate their relationship. Mac-1 and LFA-1 have distinct cellular distributions, MAb-defined antigenic determinants and α-subunits, but have highly homologous or identical β-subunits as shown by tryptic peptide mapping. Moreover, they share some common antigenic determinants recognized by a polyclonal antiserum. Cross-linking studies show that in each antigen the subunits are noncovalently associated in α₁β₁ structures. Mac-1 and LFA-1 comprise a novel family of two-chain leukocyte differentiation antigens.