Since encounters of thymocytes with the self-peptides in thymus is random, a candidate TCR cannot be exposed to the entirity of P self-peptide repertoire.Quorum sensing (Peripheral tolerance)
Since encounters of thymocytes with the self-peptides in thymus is random, a candidate TCR cannot be exposed to the entirity of P self-peptide repertoire.
There must be self-reactive peptides in mature T cell repertoire. How bad a problem is this?
Enrichment of weakly binding aminoacid during negative selection implies that the chance of activation against a random peptide is small.
Estimate based on extreme value distribution, gives the probability of activiation after selection from M self-peptides as,
Assume that a fraction M/P~0.7 of all possibly presented self-peptides P are encountered in the thymus;
The resulting in a self-activation probability is reduced to
A large repertoire to T cells is thus needed to detect a pathogen peptide
How do T cells mount an effective response to foreign epitopes while suppressing self-reactive T cells?
proposed that immune response requires collective decision (quorum) of Q T cells:
_!.jpeg)
Peripheral tolerance mechanism- Regulatory T cells (Tregs):
Subsequent validation: M. Polonsky et al, Science 360, 6394 (2018) (offline)
Informatic analysis indicates that TCRs can be distinguishes as a repertoire (set), but not individually:
