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bioRxiv · 10.1101/2023.03.29.533758

Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.

Shcherbinin, D. S.·Karnaukhov, V. K.·Zvyagin, I. V.·Chudakov, D. M.·Shugay, M.
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Abstract

T-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. A large number of TCR sequences specific to different antigens are known to date, however, the structural data describing the conformation and contacting residues for TCR:antigen:MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate template-based modeling of TCR:antigen:MHC complexes using TCR sequences with known specificity. Using the set of 29 complex templates (including a template with SARS-CoV-2 antigen) and 732 specificity records, we built a database of 1585 model structures carrying substitutions in either TCR or TCR{beta} chains with some models representing the result of different mutation pathways for the same final structure. This database allowed us to analyze features of amino acid contacts in TCR:antigen interfaces that govern antigen recognition preferences and interpret these interactions in terms of physicochemical properties of interacting residues. Our results provide a methodology for creating high-quality TCR:antigen:MHC models for antigens of interest that can be utilized to predict TCR specificity.

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Shcherbinin, D. S., Karnaukhov, V. K., Zvyagin, I. V., Chudakov, D. M., Shugay, M.. 2023-04-01. Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.. https://doi.org/10.1101/2023.03.29.533758

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