Inhibition of entire myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats by major histocompatibility complex class II-binding competitor peptides.
Previous studies have shown that major histocompatibility complex (MHC) blockade by competitor peptides with high MHC class II binding affinity can prevent peptide-induced experimental autoimmune encephalomyelitis (EAE). However, none of these studies addressed the question whether this approach could also be used to prevent EAE induced with a multivalent antigen. In this report we show the effect of competitor peptides co-immunized during EAE induction with entire guinea pig myelin basic protein (MBP) in Lewis rats. As MHC class II binding competitor peptides we used one nonimmunogenic disease-nonrelated peptide, and two immunogenic peptides, one EAE-related and one non-EAE-related. The respective efficacy of these three competitor peptides to inhibit MBP-induced proliferation of an encephalitogenic T cell line in vitro correlated with their respective MHC binding affinity. Co-immunization of the competitor peptides during disease induction with entire MBP resulted in a competitor concentration-dependent inhibition of clinical signs of EAE. These results demonstrate that, although polyclonal T cell responses to MBP were not completely inhibited, co-administration of immunogenic or nonimmunogenic either EAE-related or non-EAE-related MHC class II binding competitor peptides can inhibit the development of EAE induced with entire MBP.
Wauben
M H
MH
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
Kozhich
A
A
Joosten
I
I
Schlief
A
A
Boog
C J
CJ
van Eden
W
W
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors* / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides