Open Seminars of the Research Group on

 

Stochasticity and Control in the Dynamics and Diversity of Immune Repertories: an Example of Multi-Cellular Co-Operation

 

Tuesday, April 25, 2017, 12:00

at the Israel Institute for Advanced Studies, Room 128

 

 

 

Interpreting the T cell receptor repertoire

 

Benny Chain (UCL)

 

The T cell repertoire consists of an ensemble of alpha and beta T cell receptor (TCR) sequences which characterize a blood or tissue sample at a particular time. We understand in detail the molecular interaction between an individual T cell receptor and its cognate peptide/MHC antigen target, but the impact of antigen exposure on the repertoire as a whole is less well understood. The problem is compounded because the stochastic nature of TCR generation results in different repertoires between individuals. We approach the problem from the perspective of classification of repertoires after immunisation with different antigens in a space indexed by all possible TCRs (we focus on CDR3 sequences, which play a major role in antigen recognition). We reduce dimensionality by decomposing each CDR3 into sets of short amino acid motifs. From a biophysical perspective, these motifs may capture conserved contact points between TCR and MHC/peptide complex. The frequency of each motif in a sample of TCRs after immunisation with a given antigen defines the repertoire in a new feature space. We use support vector machines and other weak learner algorithms to identify set of features which correctly classify repertoires from different immunisations. The results suggest that immunisation induces widespread changes in the TCR repertoire distributed over a large number of individual TCRs. Short amino acid motifs, often situated at the ends of the CDR3 region, confer degenerate antigen specificity in the context of a highly diverse and largely private set of T cell receptors.

 

 

Related Research Questions

 

  1. How does the T cell receptor repertoire reflect the antigen specific response?
  2. Is T cell receptor recognition dependent on interaction of small linear sequences within the CDR3s?
  3. Can the T cell repertoire act as biomarker for infection?

 

 

Suggested Reading

 

n/a

 

 

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