Prominent usage of V beta 8.3 T cells in the H-2Db-restricted response to an influenza A virus nucleoprotein epitope.
The spectrum of TCR usage has been analyzed for virus-specific CD8+ T cells isolated from the regional mediastinal lymph modes and from the lung by bronchoalveolar lavage (BAL) of C57BL/6 (B6) mice with influenza pneumonia. Lymphocytes were recovered during the acute phase of the primary response in mice infected with an H3N2 (A/HKx31) virus, or in immune animals that were secondarily challenged with an H1N1 virus (A/PR8). Cells taken directly from the BAL of infected mice exhibited an increase in the frequency of V beta 8.3+/CD8+ T cells. In addition, 20 to 50% of proliferating CD8+ T cells in the mediastinal lymph nodes and BAL populations stimulated in vitro with A/HKx31 were V beta 8.3 TCR+. These observations indicated that the V beta 8.3+/CD8+ T cells were specifically involved in the inflammatory process during influenza infection. However, in vivo depletion of V beta 8+ T cells in CD4-depleted mice did not adversely affect viral clearance, suggesting that other CD8+ T cells can compensate for the absence of these cells. The spectrum of TCR usage was also analyzed for influenza-specific T cell hybridomas derived from freshly isolated BAL of mice with pneumonia. Many of these T cell hybridomas were V beta 8.3+, although other TCR V beta elements were used. All of the V beta 8.3+ hybridomas recognized the H-2Db-restricted NP epitope, 365-380. Although the V beta 8.3 TCR contain similar TCR D beta and J beta elements, V alpha usage was surprisingly variable. Therefore, recognition of this particular epitope was dominated by the beta-chain of the TCR. We conclude that the murine CD8+ response to influenza A virus infection of B6 mice is limited in terms of the diversity of the responding T cells. However, there is significant plasticity in the CD8+ response, which readily compensates for the absence of the dominant T cell population.
Deckhut
A M
AM
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Allan
W
W
McMickle
A
A
Eichelberger
M
M
Blackman
M A
MA
Doherty
P C
PC
Woodland
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis*; D000939:Epitopes; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D009980:Influenza A virus / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D016601:RNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D016827:CD8 Antigens; D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014758:Viral Core Proteins