T‐cell receptor affinity in the age of cancer immunotherapy

The strength of the interaction between T‐cell receptors (TCRs) and their ligands, peptide/major histocompatibility complex complexes (pMHCs), is one of the most frequently discussed and investigated features of T cells in immuno‐oncology today. Although there are many molecules on the surface of T cells that interact with ligands on other cells, the TCR/pMHC is the only receptor‐ligand pair that offers antigen specificity and dictates the functional response of the T cell. The strength of the TCR/pMHC interaction, along with the environment in which this interaction takes place, is key to how the T cell will respond. The TCR repertoire of T cells that interact with tumor‐associated antigens is vast, although typically of low affinity. Here, we focus on the low‐affinity interactions between TCRs from CD8+ T cells and different models used in immuno‐oncology.