title: Pleiotropic effects of post-translational modifications on the fate of viral glycopeptides as cytotoxic T cell epitopes.
abstract: The fate of viral glycopeptides as cytotoxic T lymphocyte (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 de-N-glycosylation, a marked decrease in major histocompatibility complex binding was observed for GP392-400 but not for GP92-101. Further, under its N-glycosylated or de-N-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.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, UMR5089 CNRS/Université Paul Sabatier, 205 route de Narbonne, 31400 Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Hudrisier
authors.forename: J
authors.initials: J
authors.lastname: Riond
authors.forename: H
authors.initials: H
authors.lastname: Mazarguil
authors.forename: J E
authors.initials: JE
authors.lastname: Gairin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000939:Epitopes; D006020:Glycopeptides; D014764:Viral Proteins