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.
Kedzierska
Katherine
K
Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
Thomas
Paul G
PG
Venturi
Vanessa
V
Davenport
Miles P
MP
Doherty
Peter C
PC
Turner
Stephen J
SJ
La Gruta
Nicole L
NL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004253:DNA Nucleotidylexotransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004253:DNA Nucleotidylexotransferase