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Abstract

The interaction between the class I major histocompatibility complex (MHC), the MHC presented peptide and the T-cell receptor (TCR) is a key determinant of the cellular immune response. This interaction is therefore of paramount importance in infectious diseases and cancer. Here, we present TCRpMHCmodels, a method for accurate structural modeling of the TCR-pMHC complex. This TCR-pMHC modeling pipeline takes as input the amino acid sequence and generates models of the TCR-pMHC complex, with a median Cα RMSD of 2.3Å. TCRpMHCmodels significantly outperforms TCRFlexDock, a specialized method for docking pMHC and TCR models. TCRpMHCmodels is simple to use and the modeling pipeline takes, on average, only 2 minutes. Thanks to its ease of use and high modeling accuracy, we expect TCRpMHCmodels to provide insights into the underlying mechanisms of TCR and pMHC interactions and as an aid in the development of advanced T-cell based immunotherapies and rational design of vaccines.