Efficient Major Histocompatibility Complex Class II-restricted Presentation of Measles Virus Relies on Hemagglutinin-mediated Targeting to Its Cellular Receptor Human CD46 Expressed by Murine B Cells By Denis Gerlier, Marie-Claude Trescol-Bi6mont,

Summary Measles virus after binding to its cell surface human CD46 receptor fuses with the plasma membrane. This fusion results in envelope hemagglutinin (H) and fusion glycoprotein (F) incorporated into the plasma membrane and injection of the nucleocapsid made of nucleoprotein (NP) into the cytosol. The influence of targeting measles virus (MV) to CD46 in the processing and presentation of MV H and NP to antigen specific MHC class II bE d- and bAd-restricted T cell hybridomas was explored using murine M12-CD46 B cell transfectants. Parent M12 cells, which lack any MV receptor, were unable to present any of these two viral proteins when incubated with MV particles. Incubating M12.CD46 cells with 200 ng and 10/zg of MV could strongly stimulate H-specific and NP-specific T cells, respectively. Neosynthesis of MV proteins was not necessary since the efficiency of antigen presentation was similar when using ultraviolet-inactivated MV. Similar enhancing effects (more than 1,000-fold) on antigen presentation were also observed when using purified native H soluble or incorporated into liposomes whereas denaturating H glycoprotein resulted in a poor efficiency in T cell stimulation, M12.CD46 being no more potent than the parental M12 counterpart. MV H and NP presentation efficiency did not depend on MV fusion with plasma membrane as revealed by the lack of effect of specific fusion inhibitors. Both MV H and NP presentations were sensitive to chloroquine inhibition indicating that antigens from CD46-mediated captured MV were likely processed in the endosome/lysosome compartment.