title: Critical residue combinations dictate peptide presentation by MHC class II molecules.
abstract: Peptides encompassing the core hen egg lysozyme HEL(52-61) peptide elongated or not and substituted or not with natural and unnatural amino acids were used to find a peptide motif for binding to the major histocompatibility complex (MHC) class II I-Ak. Using a T-cell recognition functional assay, nine out of 10 positions were found to be somehow involved in the I-Ak binding, and six out of 10 residues were involved in T-cell recognition. The deleterious effect of single substitutions could be rescued by changing peptide length and/or sequence. Thus, efficient binding to MHC class II molecules requires not only few anchoring residues correctly interspaced, but a complex, nonrandom combination of residues with appropriate orientation of the peptide backbone and some crucial side chains.
authors.affiliation: Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Université Lyon I, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Hernandez
authors.forename: F
authors.initials: F
authors.lastname: Cretin
authors.forename: S
authors.initials: S
authors.lastname: Lombard-Platet
authors.forename: J P
authors.initials: JP
authors.lastname: Salvi
authors.forename: N
authors.initials: N
authors.lastname: Walchshofer
authors.forename: D
authors.initials: D
authors.lastname: Gerlier
authors.forename: J
authors.initials: J
authors.lastname: Paris
authors.forename: C
authors.initials: C
authors.lastname: Rabourdin-Combe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D000949:Histocompatibility Antigens Class II / Q000097:blood / Q000737:chemistry*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000032:analysis*; D010446:Peptide Fragments / Q000032:analysis*; D010455:Peptides / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010455:Peptides; C090016:hen egg lysozyme peptide (52-61); D009113:Muramidase