Structural and Biophysical Characterization of Cancer-Relevant T Cell Receptor–Peptide/MHC Interactions

T cells are a critical component of the immune system that recognize pathogen-associated peptides presented on cell surfaces by major histocompatibility complex (MHC) proteins. T cells can also recognize tumor-associated or tumor-specific peptide/MHCs on cancer cells. The ability of T cells to recognize cancer establishes the basis for immunotherapies, which are approaches in which living immune cells infiltrate the tumor and kill tumor cells. Though immunotherapy has led to promising clinical results, there remains much room for improvement.

The binding event between a T cell receptor (TCR) protein and a peptide/MHC is the primary signal for initiating a T cell mediated immune response. Therefore, the ability to accurately predict TCR–peptide/MHC interactions is critical for improving existing immunotherapies by identifying target peptide/MHCs on tumor cells and avoiding off-target peptides on healthy cells. Herein, we aim to demonstrate the utility of structural and biophysical considerations in assessing TCR–peptide/MHC interactions relevant to cancer to support structure-based predictions of immunotherapy.