title: Antigenic peptides containing large PEG loops designed to extend out of the HLA-A2 binding site form stable complexes with class I major histocompatibility complex molecules.
abstract: Recognition of peptides bound to class I major histocompatibility complex (MHC) molecules by specific receptors on T cells regulates the development and activity of the cellular immune system. We have designed and synthesized de novo cyclic peptides that incorporate PEG in the ring structure for binding to class I MHC molecules. The large PEG loops are positioned to extend out of the peptide binding site, thus creating steric effects aimed at preventing the recognition of class I MHC complexes by T-cell receptors. Peptides were synthesized and cyclized on polymer support using high molecular weight symmetrical PEG dicarboxylic acids to link the side chains of lysine residues substituted at positions 4 and 8 in the sequence of the HLA-A2-restricted human T-lymphotrophic virus type I Tax peptide. Cyclic peptides promoted the in vitro folding and assembly of HLA-A2 complexes. Thermal denaturation studies using circular dichroism spectroscopy showed that these complexes are as stable as complexes formed with antigenic peptides.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Harvard University, Cambridge, MA 02138, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bouvier
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D015195:Drug Design; D004355:Drug Stability; D016356:Gene Products, tax / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000941:Antigens; D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D011092:Polyethylene Glycols