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.