Linking T cell receptor sequence to T cell function

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T cells are critical effector cells of the adaptive immune system which recognize foreign antigen in the form of peptides presented by host cell major histocompatibility complexes (MHC). Each T cell bears a unique antigen recognition receptor, the T cell receptor (TCR), which determines the exquisite specificity and the affinity with which an individual T cell binds peptide-MHC. The TCR is generated through rearrangement of germline encoded gene segments and the addition of non-templated (non-germline encoded) nucleotides by an enzyme called terminal deoxynucleotidyl transferase (TdT). The interaction strength between the TCR and peptide-MHC is a critical parameter in all T cell fate decisions, from selection in the thymus during development to differentiation during infection. Yet, due to the enormous diversity of TCRs that can be made (>10