Stabilization of peptide guinea pig myelin basic protein 72-85 by N-terminal acetylation-implications for immunological studies.
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.
de Haan
Ellen C
EC
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands.
Wauben
Marca H M
MH
Wagenaar-Hilbers
Josée P A
JP
Grosfeld-Stulemeyer
Mayken C
MC
Rijkers
Dirk T S
DT
Moret
Ed E
EE
Liskamp
Rob M J
RM
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
D004676:Myelin Basic Protein; D010446:Peptide Fragments; C118872:myelin basic protein 72-85; D005973:Glutamine; D000123:Acetyltransferases; D011761:Pyrrolidonecarboxylic Acid