The human non-lineage antigen CD46 (HuLy-m5) and primate retroviral gp70 molecules share protein-defined antigenic determinants.

The CD46 lymphocyte surface antigen of man (until recently called HuLy-m5), and defined by the E4.3 monoclonal antibody (MoAb), shares cross-reactive antigenic epitopes with the envelope gp70 glycoproteins of gibbon ape leukaemia virus (GaLV) and Mason Pfizer monkey virus (MPMV) primate retroviruses. It is now shown that the cross-reactive antigenic epitope shared by these three molecules is determined solely by the protein portion of these glycoproteins, and that the N-linked and O-linked carbohydrate moieties of these glycoproteins do not directly or sterically contribute to the antigenic cross-reactivity. When CD46 molecules (mol.wt = 66 and 56 kDa) from human thymocytes were stripped of sialic acid with neuraminidase, or stripped of N-linked carbohydrate with endoglycosidase F, the E4.3 MoAb was still able to bind and immunoprecipitate the protein core of CD46 (mol.wt = 56 and 44 kDa). Similarly, polyclonal antisera to GaLV and MPMV precipitated deglycosylated CD46, although at a reduced efficiency. The cross-reacting E4.3 MoAb, anti-GaLV and anti-MPMV antisera also immunoprecipitated HuLy-m5 primary translation protein lacking N- or O-linked carbohydrate from the in vitro translation products of human thymocyte mRNA. Thus, the antigenic cross-reactivity of CD46 molecules with GaLV gp70 and MPMV gp70 is both specific and due to protein structure rather than to carbohydrate; the findings suggest that retroviruses may have acquired a functional epitope from human CD46 or that an endogenous retroviral sequence of human may partially or completely encode the CD46 antigen.