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

Katherine Kedzierska, Paul G. Thomas, Vanessa Venturi, Miles P. Davenport, Peter C. Doherty, Stephen J. Turner, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2556-2562
Number of pages7
JournalJournal of Immunology
Volume181
Issue number4
DOIs
Publication statusPublished - 15 Aug 2008
Externally publishedYes

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