The human cell-surface glycoproteins HuLy-m5, membrane co-factor protein (MCP) of the complement system, and trophoblast leucocyte-common (TLX) antigen, are CD46.
The non-lineage restricted human CD46 antigen, with two glycoproteins of 56,000 molecular weight (MW) and 66,000 MW, was defined using a panel of monoclonal antibodies (mAb) that included the E4.3 mAb to the HuLy-m5 antigen. Here the E4.3 mAb is used to show that two other human cell-surface molecules, membrane co-factor protein (MCP) of the complement system and trophoblast leucocyte-common antigen (TLX), are the same as HuLy-m5; thus, these three independently identified molecules are equivalently CD46. A mouse mAb to TLX (H316) and a specific rabbit antiserum to purified MCP (RA-MCP) blocked the binding of FITC-labelled E4.3 to the surface of human peripheral blood leucocytes (PBL). In sequential immunoprecipitation studies, E4.3 cleared all molecules detected by H316 and the RA-MCP antiserum. Immunoprecipitation from Chinese hamster ovary cells expressing transfected MCP cDNA showed that E4.3 detects both the mature 66,000 higher MW form of MCP and its 48,000 MW pro-MCP precursor, which lacks O-linked carbohydrate and bears only simple high-mannose-type N-linked carbohydrate. The IgG fraction of a polyclonal antiserum to purified MCP blocked factor I-mediated cleavage of C3b, whereas the E4.3 mAb did not. These data establish that three independently identified antigen systems are indeed the same: HuLy-m5, which shares a cross-reactive epitope with some primate retroviral gp 70 molecules and can be physically associated with class I major histocompatibility complex (MHC) chains in the cell membrane; MCP, of interest as a member of the regulators of complement activation gene family thought to protect autologous cells from complement activation; and TLX, a polymorphic molecule of interest for its potential role at the foeto-maternal tissue interface during pregnancy. Thus, the human CD46 antigen amalgamates the HuLy-m5, MCP and TLX cell-membrane glycoproteins.
Purcell
D F
DF
Department of Pathology, University of Melbourne, Parkville, Australia.
McKenzie
I F
IF
Lublin
D M
DM
Johnson
P M
PM
Atkinson
J P
JP
Oglesby
T J
TJ
Deacon
N J
NJ
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001324:Autoantigens / Q000145:classification / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D006801:Humans; D007519:Isoantigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; C497857:CD46 protein, human; D007519:Isoantigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; C055067:trophoblast-lymphocyte cross-reactive antigens