Title : T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial
peptides
Abstract :
- Environmental factors account for 75% of the risk of developing multiple sclerosis (MS)
- Numerous infections have been suspected as environmental disease triggers, but none of them has consistently been incriminated, and it is unclear how so many different infections may play a role
- We show that a microbial peptide , common to several major classes of bacteria, can induce MS-like disease in humanized mice by crossreacting with a T cell receptor ( TCR ) that also recognizes a peptide from myelin basic protein , a candidate MS autoantigen
- Structural analysis demonstrates this crossreactivity is due to structural mimicry of a binding hotspot shared by self and microbial antigens, rather than to degenerate TCR recognition
- Biophysical studies reveal that the autoreactive TCR binding affinity is markedly lower for the microbial (mimicry) peptide than for the autoantigenic peptide
- Thus, these data suggest a possible explanation for the difficulty in incriminating individual infections in the development of MS