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SUMMARY:Randomly made yet ordered: T cell receptor and cell receptor and f
 unctional repertoires - Dr. Nir Friedman from the Weizmann Institute of Sc
 ience\, Israel 
DTSTART:20120903T133000Z
DTEND:20120903T143000Z
UID:TALK39467@talks.cam.ac.uk
CONTACT:Dr Tennie Videler
DESCRIPTION:The adaptive immune system relies on randomness\, in generatin
 g a huge and diverse set of lymphocyte receptors through random DNA rearra
 ngements. Randomness occurs also at the level of gene expression\, which w
 as shown to be a stochastic process at the molecular level. We study the i
 nterplay between randomness at the molecular level and reliable function o
 f the immune system at the cellular and multi-cellular level\, focusing on
  two cases: the T cell receptor repertoire\, and differentiation of naïve
  CD4 T cells. Although the T cell receptor (TCR) repertoire is produced by
  a random process\, studies during the years identified biases in the repe
 rtoire\, for example the unequal usage of V and J gene segments. However\,
  the mechanisms that govern such biases remain poorly understood. Using a 
 quantitative high-throughput TCR sequencing approach applied to murine T c
 ells\, we observe a very high level of similarity in various properties of
  the repertoire between individual\, genetically identical mice. This simi
 larity suggests that common underlying mechanisms determine repertoire str
 ucture. We revealed one such mechanism\, showing that chromatin conformati
 on at the DJ&#946\; genomic locus explains most of the biases observed in 
 J&#946\; usage. Remarkably\, chromatin conformation also explains J&#946\;
  usage biases measured previously in human T cells. We demonstrate that as
  a consequence of these structural and other biases\, the TCR repertoire\,
  despite its random and highly diverse nature\, contains a surprisingly la
 rge number of public sequences that are shared among individuals. We deriv
 e a necessary mathematical condition for this surprising finding\, which i
 ndicates that the TCR repertoire contains a "core” set of receptor seque
 nces that are abundant among individuals. We will present also implication
 s of stochasticity in gene expression for Th1-Th2 differentiation\, follow
 ing experiments in which we mapped cell decisions under mixed input condit
 ions.
LOCATION:Max Perutz lecture theater\, MRC-LMB\, Addenbrooke's site\, Hills
  Road
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