Environmental triggers of MS

Reynolds CJ, Sim MJ, Quigley KJ, Altmann DM, Boyton RJ.
Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease. J Neuroinflammation. 2015;12:91

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.

In this study they take a mouse that has a HLA-DR and a T cell receptor specific for myelin basic protein and they inject peptides from a slime mould and it induces EAE, so an example how autoimmunity can result from cross-reactivity to an environmental trigger. 

To be clear, they interpret this as proof of principle rather than specific evidence that exposure to slime mold sequences are pathogenic in clinical MS: the TCR stimulated by this peptide is not a public receptor across MS patients in general, and therefore, one would not generalize a case based on its specific cross-reactivities. Sequencing of the TCR repertoire from MS patients has demonstrated substantial diversity in myelin epitope-specific disease-implicated receptors. Clearly, a further caveat in considering the implications of environmental cross-reactivities is that of predicted epitopes; not all could actually stimulate T cells in this model, and not all peptides that could stimulate could induce disease. This an example where a wider environment can trigger MS-like disease