Formaldehyde inactivation of measles virus abolishes CD46-dependent presentation of nucleoprotein to murine class I-restricted CTLs but not to class II-restricted helper T cells

Abstract

To induce an MHC-restricted specific CTL or Th response, an antigen must be delivered into the appropriate cellular compartment. We explored the role of CD46 in the presentation of measles virus (MV) nucleoprotein (NP) to murine NP-specific and MHC Class I-restricted polyclonal CTLs and the effect of inactivating MV by uv or formaldehyde. CD46-- and CD46+-transfected murine cells were used as target cells. After MV infection, only the targets which expressed CD46 were lysed by NP-specific class I-restricted CTLs. When MV was uv-inactivated, NP presentation by MHC class I molecules was retained but could be blocked of fusion inhibitors which block virus cell entry. When MV was inactivated with formaldehyde, NP was no longer presented by MHC class I molecules, although it was still presented by MHC class II molecules to a NP-specific class lI-restricted T cell hybridoma. These data show that MV binding to the CD46 molecule is a prerequisite for virus-to-cell fusion and that cytosolic delivery of NP is necessary for presentation by class I molecules. Moreover, formaldehyde inactivation of virus induces the loss of class I-restricted presentation of NP due to selective abrogation of fusion and cytosolic delivery of NP. © 1995 Academic Press, Inc.