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Frontiers Media, Frontiers in Physiology, (12), 2021

DOI: 10.3389/fphys.2021.730908

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Predicting T Cell Receptor Antigen Specificity From Structural Features Derived From Homology Models of Receptor-Peptide-Major Histocompatibility Complexes

Journal article published in 2021 by Martina Milighetti ORCID, John Shawe-Taylor, Benny M. Chain
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

The physical interaction between the T cell receptor (TCR) and its cognate antigen causes T cells to activate and participate in the immune response. Understanding this physical interaction is important in predicting TCR binding to a target epitope, as well as potential cross-reactivity. Here, we propose a way of collecting informative features of the binding interface from homology models of T cell receptor-peptide-major histocompatibility complex (TCR-pMHC) complexes. The information collected from these structures is sufficient to discriminate binding from non-binding TCR-pMHC pairs in multiple independent datasets. The classifier is limited by the number of crystal structures available for the homology modelling and by the size of the training set. However, the classifier shows comparable performance to sequence-based classifiers requiring much larger training sets.