TCRpair: prediction of functional pairing between HLA-A*02:01-restricted T-cell receptor α and β chains.

Abstract

The ability of a T cell to recognize foreign peptides is defined by a single α and a single β hypervariable complementarity determining region (CDR3), which together form the T-cell receptor (TCR) heterodimer. In ∼30-35% of T cells, two α chains are expressed at the mRNA level but only one α chain is part of the functional TCR. This effect can also be observed for β chains, although it is less common. The identification of functional α/β chain pairs is instrumental in high-throughput characterization of therapeutic TCRs. TCRpair is the first method that predicts whether an α and β chain pair forms a functional, HLA-A*02:01 specific TCR without requiring the sequence of a recognized peptide. By taking additional amino acids flanking the CDR3 regions into account, TCRpair achieves an AUC of 0.71. TCRpair is implemented in Python using TensorFlow 2.0 and is freely available at https://www.github.com/amoesch/TCRpair. Supplementary data are available at Bioinformatics online.