The ectodomain of measles virus envelope glycoprotein does not gain access to the cytosol and MHC class I presentation pathway following virus-cell fusion

1 Immunobiologie Moléculaire, CNRS, UMR 49, École Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France 2 Immunité et Infections Virales, IVMC, CNRS-UCBL, UMR 5537, Faculté de Médecine Lyon R. T. H. Laënnec, 69372 Lyon Cedex 08, France 3 INSERM U 404 ‘Immunity and Vaccination’, Institut Pasteur de Lyon, Avenue Tony-Garnier, 69365 Lyon Cedex 07, France To unravel the intracellular fate of measles virus (MV) haemagglutinin (H) following fusion of the virus envelope with the cell membrane, its presentation by MHC molecules to T cells was explored. After MV infection, murine cells expressing CD46 were lysed by MHC class I-restricted CD8 CTLs specific for the ectodomain of H. In contrast, when sensitized with UV-inactivated MV, they were not lysed by these effectors, but were recognized by H-specific and class II-restricted CD4 CTLs. Thus, after MV binding and fusion, H becomes associated with plasma membrane and its ectodomain can reach the endosomal MHC-II but not the cytosolic MHC-I antigen presentation pathway. From these data and a reappraisal of previous reports, it appears that the ectodomains of both MV haemagglutinin fusion proteins, having undergone the fusion step, are not translocated into the cytosol and end up in the endosomes. Received 17 April 1996; accepted 16 July 1996.