Quorum sensing
Central tolerance and Peripheral tolerance
Having survived negative selection against M self-peptides, the chance of activation against a random peptide is small
A large repertiore to T cells is thus needed to detect a pathogen peptide
Since thymic selection is stochastic, a given TCR cannot be exposed to the entire self-peptide reperoire,
Assume that a fraction M/P of all possible self-peptides P are encountered in the thymus;
The resulting in a self-activation probability is reduced to
Given the large number of T cells, the chance of non-self-reactivity is small!
T.C. Butler, MK, & A.K. Chakraborty, PNAS 110, 11835 (2013)
propose that immune response requires collective decision of Q T cells:
Recent validation: M. Polonsky et al, Science 360, eaaj1853 (2018) (offline)