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T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide–MHC complexes

The antigen specificity of T cells is conferred by the TCR’s highly variable complementarity-determining regions (CDRs), which interact with the pMHC4. Cellular immunity requires a pool of naive T cells (the T-cell repertoire) that can recognize a multitude of potential pMHC antigens that may originate from infections or cellular transformation. If a given TCR could recognize only a single combination of peptide and MHC, an individual would need >1015 CD8+ T cells to provide efficient coverage of all potential foreign peptides, whereas it is estimated that an individual has only around 107–108 different T cells5–7. The promiscuity of TCRs allows the recognition of numerous different pMHCs by each T cell, which broadens the recognition space and ensures the effective recognition of most possible targets.
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