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
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
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.'