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Deconstructing the Peptide Specificity of TCR Recognition

T cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for the treatment of cancer where they are key components of new cellular therapies as well as soluble biologics. Although in many ways similar to antibodies, TCRs differ in the complexity of the receptor‐ligand interface: whereas antibodies can be elicited to almost any antigens, TCRs are restricted to linear peptides presented by class I or class II MHC proteins. Additionally, TCRs do not undergo affinity maturation, and bind with weak‐to‐moderate affinities and reduced specificity.