Terminal deoxynucleotidyltransferase is required for the establishment of private virus-specific CD8 ⁺ TCR repertoires and facilitates optimal CTL responses

Virus-immune CD8 ⁺ TCR repertoires specific for particular peptide-MHC class I complexes may be substantially shared between (public), or unique to, individuals (private). Because public TCRs can show reduced TdT-mediated N-region additions, we analyzed how TdT shapes the heavily public (to D ^b NP ₃₆₆ ) and essentially private (to D ^b PA ₂₂₄ ) CTL repertoires generated following influenza A virus infection of C57BL/6 (B6, H2 ^b ) mice. The D ^b NP ₃₆₆ -specific CTL response was virtually clonal in TdT ^-/- B6 animals, with one of the three public clonotypes prominent in the wild-type (wt) response consistently dominating the TdT ^-/- set. Furthermore, this massive narrowing of TCR selection for D ^b NP ₃₆₆ reduced the magnitude of D ^b NP ₃₆₆ -specific CTL response in the virus-infected lung. Conversely, the D ^b PA ₂₂₄ -specific responses remained comparable in both magnitude and TCR diversity within individual TdT ^-/- and wt mice. However, the extent of TCR diversity across the total population was significantly reduced, with the consequence that the normally private wt D ^b PA ₂₂₄ -specific repertoire was now substantially public across the TdT ^-/- mouse population. The key finding is thus that the role of TdT in ensuring enhanced diversity and the selection of private TCR repertoires promotes optimal CD8 ⁺ T cell immunity, both within individuals and across the species as a whole.