title: Steric recognition of T-cell receptor contact residues is required to map mutant epitopes by immunoinformatical programmes.
abstract: MHC class I-restricted CD8 T-lymphocyte epitopes comprise anchor motifs, T-cell receptor (TCR) contact residues and the peptide backbone. Serial variant epitopes with substitution of amino acids at either anchor motifs or TCR contact residues have been synthesized for specific interferon-γ responses to clarify the TCR recognition mechanism as well as to assess the epitope prediction capacity of immunoinformatical programmes. CD8 T lymphocytes recognise the steric configuration of functional groups at the TCR contact side chain with a parallel observation that peptide backbones of various epitopes adapt to the conserved conformation upon binding to the same MHC class I molecule. Variant epitopes with amino acid substitutions at the TCR contact site are not recognised by specific CD8 T lymphocytes without compromising their binding capacity to MHC class I molecules, which demonstrates two discrete antigen presentation events for the binding of peptides to MHC class I molecules and for TCR recognition. The predicted outcome of immunoinformatical programmes is not consistent with the results of epitope identification by laboratory experiments in the absence of information on the interaction with TCR contact residues. Immunoinformatical programmes based on the binding affinity to MHC class I molecules are not sufficient for the accurate prediction of CD8 T-lymphocyte epitopes. The predictive capacity is further improved to distinguish mutant epitopes from the non-mutated epitopes if the peptide-TCR interface is integrated into the computing simulation programme.
authors: Vaccine Research and Development Centre, National Health Research Institute, Miaoli County, Taiwan.
authors: Shiou-Chih
authors: SC
authors: Hsu
authors: Chih-Peng
authors: CP
authors: Chang
authors: Chao-Yuan
authors: CY
authors: Tsai
authors: Shih-Hung
authors: SH
authors: Hsieh
authors: Betty A
authors: BA
authors: Wu-Hsieh
authors: Yu-Shu
authors: YS
authors: Lo
authors: Jinn-Moon
authors: JM
authors: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019295:Computational Biology; D018604:Epitope Mapping; D005805:Genes, MHC Class I / Q000276:immunology; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D020539:Sequence Analysis, Protein; D012984:Software
chemical_list: D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell