Self and non-self peptides treat autoimmune encephalomyelitis: T cell anergy or competition for major histocompatibility complex class II binding?
In susceptible strains of mice, myelin basic protein (MBP) peptide Acl-ll induces experimental autoimmune encephalomyelitis (EAE) providing a useful model for human multiple sclerosis. Acl-11 binds major histocompatibility complex (MHC) class II molecules A alpha upsilon A beta upsilon. Here, we show that the Acl-11 peptide, when administered intraperitoneally in incomplete Freund's adjuvant (IFA) emulsion, can effectively treat Acl-11-induced EAE in mice. Treatment with Acl-11/IFA 9 days after initial immunization with Acl-11 in complete Freund's adjuvant (CFA) results in a loss of T cell proliferation to MBP Acl-11. This lack of T cell proliferation is not due to T cell anergy and is not specific. A similar lack of T cell proliferation and inhibition of EAE is observed when an ovalbumin peptide OVA323-339 or a sperm whale myoglobin peptide SWM110-121 are used to treat mice immunized with Acl-11. Interestingly, we show that previously unresponsive lymph node cells from treated mice respond normally if Acl-11 is presented by fresh antigen-presenting cells taken from normal mice. These results argue that the lack of T cell proliferation and inhibition of EAE is not due to specific T cell anergy as suggested by others. Instead this appears to be due to blocking of MHC class II molecules A alpha upsilon A beta upsilon by the treating peptides.
Gautam
A M
AM
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001667:Binding, Competitive; D017635:Clonal Anergy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; D010047:Ovalbumin