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bioRxiv · 10.1101/693630

Comprehensive analysis of structural and sequencing data reveals almost unconstrained chain pairing in TCRαβ complex

Shcherbinin, D. S.·Belousov, V. A.·Shugay, M.
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Abstract

Antigen recognition by T-cells is guided by the T-cell receptor (TCR) heterodimer formed by and {beta} chains. A huge diversity of TCR sequences should be maintained by the immune system in order to be able to mount an effective response towards foreign pathogens, so, due to cooperative binding of and {beta} chains to the pathogen, any constraints on chain pairing can have a profound effect on immune repertoire structure, diversity and antigen specificity. By integrating available structural data and paired chain sequencing results we were able to show that there are almost no constraints on pairing in TCR{beta} complexes, allowing naive T-cell repertoire to reach the highest possible diversity. Additional analysis reveals that the specific choice of contacting amino acids can still have a profound effect on complex conformation. Moreover, antigen-driven selection can distort the uniform landscape of chain pairing, while small, yet significant, differences in the pairing can be attributed to various specialized T-cell subsets such as MAIT and iNKT T-cells, as well as other putative invariant TCRs.

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Shcherbinin, D. S., Belousov, V. A., Shugay, M.. 2019-07-05. Comprehensive analysis of structural and sequencing data reveals almost unconstrained chain pairing in TCRαβ complex. https://doi.org/10.1101/693630

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