Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8+ T cell immunodominance hierarchies

J Immunol. 2008 Jul 1;181(1):649-59. doi: 10.4049/jimmunol.181.1.649.

Abstract

The action of TdT on mouse TCR genes accounts for approximately 90% of T cell repertoire diversity. We report that in TdT-/- mice, total T(CD8+) responses to influenza and vaccinia viruses are reduced by approximately 30% relative to wild-type mice. We find that T(CD8+) responses to three subdominant influenza virus determinants are reduced to background values in TdT-/- mice while responses to three immunodominant determinants undergo a major reshuffling. A similar reshuffling occurs in T(CD8+) responses to immunodominant vaccinia virus determinants, and is clearly based on broad differences in TCR family usage and CDR3 length between wild-type and TdT-/- mice. These findings demonstrate that TdT plays a critical role in the magnitude and breadth of anti-viral T(CD8+) responses toward individual determinants and suggests that germline TCR repertoire bias toward the most dominant determinants is a major factor in establishing immunodominance hierarchies.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology*
  • DNA Nucleotidylexotransferase / deficiency
  • DNA Nucleotidylexotransferase / genetics
  • DNA Nucleotidylexotransferase / immunology*
  • DNA Nucleotidylexotransferase / metabolism*
  • Female
  • Influenza A virus / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / immunology
  • Vaccinia virus / immunology

Substances

  • Antigens, Viral
  • Receptors, Antigen, T-Cell
  • DNA Nucleotidylexotransferase