Design and synthesis of a cyclic double mutant peptide (cyclo(87-99)[A91,A96]MBP87-99) induces altered responses in mice after conjugation to mannan: implications in the immunotherapy of multiple sclerosis.
Altered peptide ligands that alter immune responses are a promising approach to the immunotherapy of multiple sclerosis. Cyclic peptides are of interest because the limited stability of linear peptides restricts their use in vivo. We designed and synthesized a cyclic double mutant peptide from MBP(87-99)-[cyclo(87-99)[A(91),A(96)]MBP(87-99)]. Immunization of mice, in CFA reduced Th1 responses. However, when conjugated to reduced mannan, a significant further reduction of Th1 responses and moderate Th2 responses were induced.
Katsara
Maria
M
Burnet Institute, Immunology and Vaccine Laboratory, Heidelberg, VIC, Australia.
Deraos
George
G
Tselios
Theodore
T
Matsoukas
Minos-Timotheos
MT
Friligou
Irene
I
Matsoukas
John
J
Apostolopoulos
Vasso
V
D000276:Adjuvants, Immunologic; D000818:Animals; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008351:Mannans / Q000737:chemistry*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D009154:Mutation / Q000235:genetics; D004676:Myelin Basic Protein / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D008351:Mannans; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D015847:Interleukin-4; D007371:Interferon-gamma