Crossreactive Epstein-Barr virus (EBV)-influenza A virus (IAV) specific CD8 memory T cells during acute symptomatic IAV infection. (VIR2P.1022)

Abstract

We previously showed that crossreactivity is common between IAV and EBV in HLA-A2+ patients during infectious mononucleosis. IAV-M1 specific CD8 T cells, along with expanded populations of IAV-M1/EBV-BRLF-1 and IAV-M1/EBV-BMLF-1 double-tetramer+ cells were detected directly ex-vivo in 5 HLA-A2+ patients. Altered IAV-M1, EBV-BRLF1 and -BMLF1 TCR repertoires were observed over the course of infection and in comparison to healthy donors. After culture, cells were sorted and analyzed by gene array in order to assess global changes in immune responses following different stimulations, either cognate or crossreactive, in different patient populations. M1- and BRLF1-specific cells had similar immune-response gene signatures, but the BMLF1-specific CD8 cells were more similar to the two-crossreactive populations. Crossreactive M1/BRLF1 cells from the BRLF1 line were different in their activation status than the BRLF1-specific cells, consistent with BRLF1 ligand stimulation of different gene activation profiles in these two populations. These results suggest that during symptomatic IAV infection there is an expansion of EBV/IAV crossreactive memory CD8 T cell responses. Ongoing studies are investigating whether EBV-IAV cross-reactive CD8+ T cells may contribute to immunopathology during acute IAV infection.