SYNCYTIUM-INHIBITING MONOCLONAL-ANTIBODIES PRODUCED AGAINST HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE 1-INFECTED CELLS RECOGNIZE CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES AND BLOCK BY PROTEIN CROWDING

Four new monoclonal antibodies (MAbs) that inhibit human T-cell lympho tropic virus type 1 (HTLV-1)-induced syncytium formation were produced by immunizing BALB/c mice with HTLV-l-infected MT2 cells. Immunopreci pitation studies and binding assays of transfected mouse cells showed that these MAbs recognize class II major histocompatibility complex (M HC) molecules. Previously produced anti-class II MHC antibodies also b locked HTLV-1-induced cell fusion. Coimmunoprecipitation and competiti ve MAb binding studies indicated that class II MHC molecules and HTLV- 1 envelope glycoproteins are not associated in infected cells. Anti-MH C antibodies had no effect on human immunodeficiency virus type 1 (HIV -l) syncytium formation by cells coinfected with HIV-1 and HTLV-1, rul ing out a generalized disruption of cell membrane function by the anti bodies. High expression of MHC molecules suggested that steric effects of bound anti-MHC antibodies might explain their inhibition of HTLV-1 fusion. An anti-class I MHC antibody and a polyclonal antibody consis ting of several nonblocking MAbs against other molecules bound to MT2 cells at levels similar to those of class II MHC antibodies, and they also blocked HTLV-1 syncytium formation. Dose-response experiments sho wed that inhibition of HTLV-1 syncytium formation correlated with leve ls of antibody bound to the surface of infected cells. The results sho w that HTLV-1 syncytium formation can be blocked by protein crowding o r steric effects caused by large numbers of immunoglobulin molecules b ound to the surface of infected cells and have implications for the st ructure of the cellular HTLV-1 receptor(s).