Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease

Background: multiple sclerosis is generally considered an autoimmune disease resulting from interaction between predisposing genes and environmental factors,together allowing immunological self-tolerance to be compromised. the precise nature of the environmental inputs has been elusive,infectious agents having received considerable attention. a recent study generated an algorithm predicting naturally occurring t cell receptor (tcr) ligands from the proteome database. taking the example of a multiple sclerosis patient-derived anti-myelin tcr,the study identified a number of stimulatory,cross-reactive peptide sequences from environmental and human antigens. having previously generated a spontaneous multiple sclerosis (ms) model through expression of this tcr,we asked whether any of these could indeed function in vivo to trigger cns disease by cross-reactive activation. findings: a number of myelin epitope cross-reactive epitopes could stimulate t cell immunity in this ms anti-myelin tcr transgenic model. two of the most stimulatory of these 'environmental' epitopes,from dictyostyelium slime mold and from emiliania huxleyi,were tested for the ability to induce ms-like disease in the transgenics. we found that immunization with cross-reactive peptide from dictyostyelium slime mold (but not from e. huxleyi) induces severe disease. conclusions: these specific environmental epitopes are unlikely to be common triggers of ms,but this study suggests that our search for the cross-reactivity triggers of autoimmune activation leading to ms should encompass epitopes not just from the 'infectome' but also from the full environmental 'exposome.' © 2015 reynolds et al.; licensee biomed central.