Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules.
In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII). In this study, we demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex with Aq molecules prevented development of CIA in mice and ameliorated chronic relapsing disease. In contrast, nonglycosylated CII259-273/Aq complexes had no such effect. CIA dependent on other MHC class II molecules (Ar/Er) was also down-regulated, indicating a bystander vaccination effect. T cells could transfer the amelioration of CIA, showing that the protection is an active process. Thus, a complex between MHC class II molecules and a posttranslationally modified peptide offers a new possibility for treatment of chronically active autoimmune inflammation such as rheumatoid arthritis.
Dzhambazov
Balik
B
Medical Inflammation Research, Lund University, Lund, Sweden.
Nandakumar
Kutty Selva
KS
Kihlberg
Jan
J
Fugger
Lars
L
Holmdahl
Rikard
R
Vestberg
Mikael
M
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D024201:Bystander Effect / Q000276:immunology; D002417:Cattle; D002908:Chronic Disease; D024043:Collagen Type II / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
D024043:Collagen Type II; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D046912:Multiprotein Complexes; D010455:Peptides; D014612:Vaccines; D005690:Galactose