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

Summary 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 retrovinises 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.