In silico specificity determination of neoantigen-reactive T-lymphocytes

Kniga A.E.1 , Polyakov I.V.1, Nemukhin A.V.1

1. M.V. Lomonosov Moscow State University, Moscow, Russia; N.M. Emanuel Institute of Biochemical Physics RAS, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20216703251      PubMed Id: 34142532
Year: 2021  Volume: 67  Issue: 3  Pages: 251-258
Effective personalized immunotherapies of the future will need to capture not only the peculiarities of the patient’s tumor but also of his immune response to it. In this study, using results of in vitro high-throughput specificity assays, and combining comparative models of pMHCs and TCRs using molecular docking, we have constructed all-atom models for the putative complexes of all their possible pairwise TCR-pMHC combinations. For the models obtained we have calculated a dataset of physics-based scores and have trained binary classifiers that perform better compared to their solely sequence-based counterparts. These structure-based classifiers pinpoint the most prominent energetic terms and structural features characterizing the type of protein-protein interactions that underlies the immune recognition of tumors by T cells.
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Keywords: neoantigen, molecular docking, protein-protein interactions, comparative modeling, machine learning, TCR-pMHC

Kniga, A. E., Polyakov, I. V., Nemukhin, A. V. (2021). In silico specificity determination of neoantigen-reactive T-lymphocytes. Biomeditsinskaya khimiya, 67(3), 251-258.
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