Evidence that prolonged antigen-driven inflammation after influenza infection helps shape the specificity of the CD8 T cell recall response (130.5)

Abstract

Influenza viruses encode four major epitopes (NP, PA, PB1 and PB2) that are recognized by naïve CD8 T cells in C57BL/6 mice. MHC class I tetramer analysis has shown that CD8 T cells specific for the NP and PA epitopes are equally represented during the response to a primary infection with the reassortant HKx31 influenza virus. Secondary challenge with the serologically distinct A/PR/8 strain, however leads to a change in the dominance hierarchy so that NP-specific cells outnumber PA-specific cells in most tissues by approximately 5:1. We recently found that processed NP antigen persists in vivo long after infectious influenza virus has been eliminated. Large numbers of endogenous NP-specific CD8 T cells in the antigen bearing lymph nodes showed signs of a response to recent antigen stimulation. In contrast, there were much smaller numbers of PA-specific CD8 T cells in the mediastinal lymph node (MLN), with a much lower frequency of activated T cells. Since DC carry viral antigens to the MLN immediately after influenza infection, we have investigated whether the local specificities of antigen-specific memory CD8 T cells in the MLN at the time of reinfection help shape the specificity of the recall response. Since there is evidence in the literature that NP epitope is more protective than PA epitope, these studies will help us to elucidate the role of antigen and the biology of local specific memory CD8 T cell response in the shaping of the CD8 T cell response during secondary infections with influenza virus. This work was supported by NIH grants AI065895 & AI071213 (LSC),