Quast, N. P. | Search bioRxiv

bioRxiv2025

STCRpy: a software suite for T cell receptor structure parsing, interaction profiling and machine learning dataset preparation

SummaryComputational methods to guide early-stage TCR drug discovery and TCR repertoire informatics currently under-utilise solved and predicted structure data. Here, we streamline use of these data through an open-source python package for high-throughput TCR structure handling and analysis (STCRpy), facilitating analyses such as TCR:peptide-MHC complex orientation calculation/scoring, root-mean-square-distance evaluation, interaction profiling, and machine learning dataset curation. Availability and implementationFreely available as a Python package at https://github.com/npqst/STCRpy. Contactdeane@stats.ox.ac.uk, raybould@stats.ox.ac.uk

immunology↗

bioRxiv2024

T-cell receptor structures and predictive models reveal comparable alpha and beta chain structural diversity despite differing genetic complexity

T-cell receptor (TCR) structures are currently under-utilised in early-stage drug discovery and repertoire-scale informatics. Here, we leverage a large dataset of solved TCR structures from Immunocore to evaluate the current state-of-the-art for TCR structure prediction, and identify which regions of the TCR remain challenging to model. Through clustering analyses and the training of a TCR-specific model capable of large-scale structure prediction, we find that the alpha chain VJ-recombined loop (CDRA3) is as structurally diverse and correspondingly difficult to predict as the beta chain VDJ-recombined loop (CDRB3). This differentiates TCR variable domain loops from the genetically analogous antibody loops and supports the conjecture that both TCR alpha and beta chains are deterministic of antigen specificity. We hypothesise that the larger number of alpha chain joining genes compared to beta chain joining genes compensates for the lack of a diversity gene segment. Overall, our study demonstrates that valuable structure-function relationships can lie in alpha chains despite their simpler junctions. We also provide over 1.5M predicted TCR structures to enable repertoire structural analysis and elucidate strategies towards improving the accuracy of future TCR structure predictors.

immunology↗