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

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.

• Authors: Katherine Kedzierska, Paul G Thomas, Vanessa Venturi, Miles P Davenport, Peter C Doherty, Stephen J Turner, Nicole L La Gruta
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 4 Pg. 2556-62 (Aug 15 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18684946 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Receptors, Antigen, T-Cell, alpha-beta
• DNA Nucleotidylexotransferase

Topics

• Animals
• CD8-Positive T-Lymphocytes (enzymology, immunology, virology)
• Clone Cells
• Cytotoxicity, Immunologic (genetics)
• DNA Nucleotidylexotransferase (deficiency, genetics, physiology)
• Epitopes, T-Lymphocyte (biosynthesis, immunology)
• Female
• Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
• Influenza A Virus, H3N2 Subtype (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Orthomyxoviridae Infections (enzymology, immunology, metabolism)
• Receptors, Antigen, T-Cell, alpha-beta (biosynthesis, genetics)
• T-Lymphocytes, Cytotoxic (enzymology, immunology, virology)