Antigenic mimicry - The key to autoimmunity in immune privileged organs

The eye and the brain are the best investigated immune privileged sites for T cell mediated autoimmune diseases, with several experimental animal models in multiple species like experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune uveitis (EAU). It was difficult to explain autoimmunity to antigens which are sequestered behind blood-organ barriers since those barriers can only be passed by already activated lymphocytes. Antigen-specific lymphocytes must therefore be activated outside of the immune privileged target organs by crossreactivity of immune receptors to similar antigens, designated as "antigenic mimicry". Crossreactivity as the basic mechanism for antigenic mimicry is generally important for the immune recognition of a huge variety of different antigens with a comparably restricted number of T cell receptors and antibodies. Here, various T cell mimotopes are discussed that can induce autoimmune diseases or immune tolerance or both. Mimotopes are antigenic epitopes with similarity to different, unrelated antigens that are not distinguished by T cell receptors. Finally, the role of the microbiome is touched briefly, it is suspected to provide many mimotopes for T cell responses that, however, are very difficult to define due to the enormous size, and individual variability of our microbiome and virome.