title: Influence of saccharide size on the cellular immune response to glycopeptides.
abstract: Glycopeptides that bind to MHC molecules on antigen presenting cells may elicit carbohydrate selective T cells. In order to investigate how the cellular immune response depends on the size of the carbohydrate moiety, a trigalactosylated derivative of an immunogenic peptide from hen egg-white lysozyme (HEL52-61) was prepared. Synthesis was accomplished by assembly of an alpha-1,4-linked trigalactose peracetate which was coupled to Fmoc serine. After activation as a pentafluorophenyl ester the resulting building block was used in solid-phase synthesis In contrast to the corresponding mono- and digalactosylated derivatives of HEL52-61, the trigalactosylated HEL52-61 was not immunogenic. Somewhat surprisingly, this was found to be because the trigalactosyl derivative bound approximately two orders of magnitude weaker to I-Ak MHC molecules than the mono- and digalactosyl peptides. Our observation suggests an explanation for previous findings, which show that glycopeptides isolated from MHC molecules in nature usually carry small saccharides.
authors.affiliation: Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Mickael
authors.initials: M
authors.lastname: Mogemark
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cirrito
authors.forename: Petter
authors.initials: P
authors.lastname: Sjölin
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.forename: Jan
authors.initials: J
authors.lastname: Kihlberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D002645:Chickens; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology; D005260:Female; D005690:Galactose / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000737:chemistry / Q000276:immunology; D009113:Muramidase / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology; D014312:Trisaccharides / Q000737:chemistry* / Q000276:immunology*
chemical_list: D004187:Disaccharides; D006020:Glycopeptides; D009005:Monosaccharides; D014312:Trisaccharides; D009113:Muramidase; D005690:Galactose