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,

estimated from extreme value distribution, as

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

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

Estimates of number of distinct T cells vary, we used an estimate T~40,000 for a particular tissue

Since thymic selection is stochastic, a given TCR cannot be exposed to the entire self-peptide repertoire,

  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 in a tissue, the chance of self-reactivity is large!

T.C. Butler, MK, & A.K. Chakraborty, PNAS 110, 11835 (2013)

proposed that immune response requires collective decision of   Q    T cells:

For Q=10

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

Also: F. Camaglia, ..., T. Mora, A. Walczak, N. Friedman, eLife 2023;12:e81622 (2023) (offline)

Onset of autoimmune diseases are correlated to persistent/severe viral infections:

Rose Yin, Samuel Melton, Eric Huseby, M.K. & Arup K Chakraborty, bioRxiv (2023) (offline)

modified the quorum model to explore this connection:

A key step in (2. ... lower activation threshold) is justified by experiments:

Probability for onset of autoimmunity increases with the number of foreign peptides presented:

The probability is dominated by encounters with rare (hydrophobic) peptides that activate many T cells

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                          

The predicted number of T cells for such quorum is