title: T cell recognition of the dominant I-A(k)-restricted hen egg lysozyme epitope: critical role for asparagine deamidation.
abstract: Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL(48-62)) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-A(k) in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL peptide and not the native peptide. The sequence of the HEL epitope facilitates rapid and spontaneous deamidation when present as a free peptide or within a flexible domain. However, this deamidated epitope is not created within intact lysozyme, most likely because it resides in a highly structured part of the protein. These findings argue against the existence of multiple conformations of the same peptide-MHC complex and have important implications for the design of peptide-based vaccines. Furthermore, as the type-B T cells are known to selectively evade induction of tolerance when HEL is expressed as a transgene, these results suggest that recognition of posttranslationally modified self-antigen may play a role in autoimmunity.
authors.affiliation: Institute of Immunology, University of Oslo, Rikshospitalet, Oslo N-0027, Norway. stephen.mcadam@labmed.uio.no
authors.forename: S N
authors.initials: SN
authors.lastname: McAdam
authors.forename: B
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: I B
authors.initials: IB
authors.lastname: Rasmussen
authors.forename: D G
authors.initials: DG
authors.lastname: Schmid
authors.forename: I
authors.initials: I
authors.lastname: Sandlie
authors.forename: B
authors.initials: B
authors.lastname: Bogen
authors.forename: N J
authors.initials: NJ
authors.lastname: Viner
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000378:metabolism*; D015551:Autoimmunity; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D001216:Asparagine; C421864:hen egg lysozyme; D009113:Muramidase