Abstract
The six complementarity determining regions (CDRs) of the T cell receptor (TCR) form multiple contacts with cognate peptide and major histocompatibility complex, thus determining antigen specificity. However, the importance of contacts between the CDRs themselves remains poorly understood. With a systematic study of over 200 unique TCR structures, we identify consistent intra and inter-chain CDR contact zones. We hypothesise that these interactions may restrict TCRα/TCRβ pairing within epitope-specific repertoires. Indeed, we show that the sequences of paired TCRα and TCRβ are not independent within the repertoires of TCRs specific for most epitopes examined. We show that this sequence restriction can be quantified using a mutual information framework, can be learnt by co-evolution models without using a training set of known pairs and allows de novo predictions of TCRα/TCRβ pairing.
Competing Interest Statement
The authors have declared no competing interest.
