Avoiding autoimmune disease – T cells know their limits

The molecular mimicry theory has become a dominant paradigm to explain the triggering of autoaggressive T lymphocytes. The basis of the theory is that an immune response is triggered by non-self during infection and subsequent cross-reactive T-cell recognition of a similar self antigen provokes an inflammatory lesion in the target organ. It is clear that we all harbour autoreactive T cells and that T-cell receptor (TCR) cross-reactivity is extensive. Here, I argue that the immune system has evolved mechanisms to limit the risk of an autoaggressive response. Importantly, the strength of TCR stimulation provided by self and non-self antigens will usually differ. Evidence points to a model in which the three pillars of immune tolerance (deletion, anergy–adaptation and regulation) act to limit autoimmune disease from molecular mimicry.