Self and non‐self peptides treat autoimmune encephalomyelitis: T cell anergy or competition for major histocompatibility complex class II binding?

• Published in: European Journal of Immunology
• Main Author: Gautam, Anand M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 1995
• Subjects: Sperm whale
• Online Access: http://dx.doi.org/10.1002/eji.1830250738; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Feji.1830250738; https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.1830250738

Abstract In susceptible strains of mice, myelin basic protein (MBP) peptide Ac1‐11 induces experimental autoimmune encephalomyelitis (EAE) providing a useful model for human multiple sclerosis. Ac1‐11 binds major histocompatibility complex (MHC) class II molecules Aα u Aβ u . Here, we show that the Ac1‐11 peptide, when administered intraperitoneally in incomplete Freund's adjuvant (IFA) emulsion, can effectively treat Ac1‐11‐induced EAE in mice. Treatment with Ac1‐11/IFA 9 days after initial immunization with Ac1‐11 in complete Freund's adjuvant (CFA) results in a loss of T cell proliferation to MBP Ac1‐11. 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 Ac1‐11. Interestingly, we show that previously unresponsive lymph node cells from treated mice respond normally if Ac1‐11 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 Aα u Aβ u by the treating peptides.