title: Stabilization of peptide guinea pig myelin basic protein 72-85 by N-terminal acetylation-implications for immunological studies.
abstract: Peptide gpMBP72-85, containing amino acids 72-85 of guinea pig myelin basic protein is commonly used to induce experimental autoimmune encephalomyelitis in Lewis rats. The N-terminal glutamine in this peptide can cyclize to pyroglutamic acid, leading to loss of the first MHC anchor for binding to MHC class II. Acetylation of the peptide N-terminus prevents pyroglutamic acid formation and ensures a constant quality. An increased MHC binding affinity after N-terminal acetylation was observed. This modification also enhanced T cell proliferation of a gpMBP reactive T cell clone. The encephalitogenicity of peptide gpMBP72-85 was unaffected by acetylation. It is concluded that acetylation improves the chemical stability of gpMBP72-85, and is not detrimental but rather favorable for its biochemical and immunological, in vitro, and in vivo behavior.
authors.affiliation: Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: de Haan
authors.forename: Marca H M
authors.initials: MH
authors.lastname: Wauben
authors.forename: Josée P A
authors.initials: JP
authors.lastname: Wagenaar-Hilbers
authors.forename: Mayken C
authors.initials: MC
authors.lastname: Grosfeld-Stulemeyer
authors.forename: Dirk T S
authors.initials: DT
authors.lastname: Rijkers
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D005973:Glutamine / Q000378:metabolism; D006168:Guinea Pigs; D006358:Hot Temperature; D008285:Major Histocompatibility Complex / Q000276:immunology / Q000502:physiology; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D004676:Myelin Basic Protein; D010446:Peptide Fragments; C118872:myelin basic protein 72-85; D005973:Glutamine; D000123:Acetyltransferases; D011761:Pyrrolidonecarboxylic Acid