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

Using an estimate of M~104  gives  p~10-4  

A large repertiore to T cells is thus needed to detect a pathogen peptide

Estimates of number of distinct T cells vary, use  T~107

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:

                          

Distinguishing between self and pathogen peptides requires

The predicted number of T cells for such quorom is

Recent validation: M. Polonsky et al, Science 360, eaaj1853 (2018)  (offline)