The Role of Serologically Defined Epitopes on Mumps Virus HN‐Glycoprotein in the Induction of Virus‐Dependent Cell‐Mediated Cytotoxicity

Abstract

The importance of virus structural proteins for the induction of virus-dependent cellular cytotoxicity (VDCC) was studied by means of monoclonal antibodies raised in mice against mumps virions. Antibodies against the viral glycoprotein bearing the haemagglutination and neuraminidase activities (HN) inhibited VDCC but not the natural cytotoxicity (NK) displayed by the lymphocytes in the absence of virus. Antibodies to the fusion factor, the membrane protein or the nucleoprotein were inactive. These results confirmed our previous conclusion, that the only viral component required for VDCC induction is the HN protein. To clarify the role of this protein in VDCC further, the inhibitory activity of 13 HN-specific monoclonals, all of IgG isotype and directed against 9 distinct determinants, was studied in detail. Seven antibodies reacting with 3 different determinants of the peptide moiety of the HN protein were strongly inhibitory. The remaining antibodies, specific for 5 additional peptide epitopes, had intermediate or weak inhibitory effects. One carbohydrate specific anti-HN antibody was inactive although its antigen-binding capacity was of the same magnitude as that of a good inhibitory antibody. The anti-HN antibodies inhibited VDCC regardless of their IgG subclass. Moreover, VDCC inhibition was not correlated with the capacity of the antibodies to inhibit haemagglutination, haemolysis, neuraminidase activity, or the infectivity of the virus. These results suggest that full expression of VDCC requires the interaction of more than one of the serologically defined structures of the HN polypeptide with virus receptors on the lymphocytes and probably also on the target cells. These structures may be different at least in part from those involved in other known biological activities of the virus. Treatment of lymphocytes with virus increases both the number of target-binding cells (TBC) and the number of cytotoxic effector cells. However, when treated under conditions which gave optimal VDCC inhibition, none of the inhibitory antibodies reduced the virus-mediated increase in TBC. This indicates either that the anti-HN antibodies decreased the efficiency of effector-target cell interaction necessary for VDCC induction, or that they blocked a post-binding step required for triggering of cytotoxicity.