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Pleiotropic effects of post-translational modifications on the fate of viral glycopeptides as cytotoxic T cell epitopes.
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Edité par CCSD ; American Society for Microbiology -
The fate of viral glycopeptides as cytotoxic T lymphocytes (CTL) epitopes is unclear. We have dissected the mechanisms of antigen presentation and CTL recognition of the peptide GP392-400 (WLVTNGSYL) from the lymphocytic choriomeningitis virus (LCMV) and compared them with those of the previously reported GP92-101 antigen (CSANNSHHYI). Both GP392-400 and GP92-101 bear a glycosylation motif, are naturally N-glycosylated in the mature viral glycoproteins, bind to major histocompatibility complex H-2D b molecules and are immunogenic. However, post-translational modifications differentially affected GP92-101 and GP392-400. Upon N-glycosylation or deN -glycosylation, a marked decrease in MHC binding was observed for GP392-400 but not for GP92-101. Further, under its Nglycosylated or deN -glycosylated form, GP392-400 then lost its initial ability to generate a CTL response in mice whereas GP92-101 was still immunogenic under the same conditions. The genetically encoded form of GP392-400, which, on the basis of its immunogenicity, could still be presented with H-2D b during the course of LCMV infection does not in fact appear at the surface of LCMV-infected cells. Our results show that post-translational modifications of viral glycopeptides can have pleiotropic effects on their presentation to and recognition by CTL that contribute to either creation of neo-epitopes or destruction of potential epitopes.
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