title: Selection of peptides that bind to the HLA-A2.1 molecule by molecular modelling.
abstract: Cytotoxic T lymphocytes recognize antigenic peptides in association with major histocompatibility complex class I proteins. Although a large set of class I binding peptides has been described, it is not yet easy to search for potentially antigenic peptides without synthesis of a panel of peptides, and subsequent binding assays. In order to predict HLA-A2.1-restricted antigenic epitopes, a computer model of the HLA-A2.1 molecule was established using X-ray crystallography data. In this model nonameric peptide sequences were aligned. In a molecular dynamics (MD) simulation with two sets of peptides known to be presented by HLA-A2.1, it was important to know the anchor amino acid residue preference and the distance between the anchor residues. We show here that the peptides bound to the HLA-A2.1 model structure possess a side chain of C-terminal anchor residue oriented into the binding groove with different distances between the two anchor residues from 15 to 21A. We also synthesized a set of nonamer peptides containing amino acid sequences of Hepatitis B virus protein that were selected on the basis of previously described HLA-A2.1 specific motifs. When results obtained from the MD simulation were compared with functional binding assays using the TAP-deficient cell line T2, it was evident that the MD simulation method improves prediction of the HLA-A2.1 binding epitope sequence. These results suggest that this approach can provide a way to predict peptide epitopes and search for antigenic regions in sequences in a variety of antigens without screening a large number of synthetic peptides.
authors.affiliation: Genetic Engineering Research Institute, Korea Institute of Science and Technology, Taejon, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: H G
authors.initials: HG
authors.lastname: Lee
authors.forename: K Y
authors.initials: KY
authors.lastname: Lee
authors.forename: T J
authors.initials: TJ
authors.lastname: Kwon
authors.forename: K
authors.initials: K
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006511:Hepatitis B Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D015789:HLA-A2 Antigen; D006511:Hepatitis B Antigens; D009842:Oligopeptides