Crossreactive influenza A virus M1- and EBV-BMLF-1-specific CD8 T cells modulate disease severity of Epstein-Barr Virus-induced infectious mononucleosis (49.20)

Abstract

Abstract During EBV-associated infectious mononucleosis (IM) influenza A-specific crossreactive memory T cells are highly activated and play a role in disease severity. In HLA-A2+ IM patients, influenza M158 (IAV-M1)-specific CD8 memory T cell responses cross-reacted with two different EBV lytic epitopes, BRLF-1(190) (19/20) and BMLF-1(280) (17/29). Furthermore, 11/22 IM patients demonstrated some intra-viral cross-reactivity between EBV-BRLF-1 and -BMLF-1 responses. Disease severity of IM did not correlate with viral load, but instead directly correlated with the percentage of IAV-M1, EBV-BMLF-1 and crossreactive IAV-M1/EBV-BMLF-1-specific CD8 T cells. This was associated with altered TCR Vbeta usage. In all IM patients cross-reactive T cell responses were observed but different patterns of cross-reactivity were seen in each individual. A number of unique features of the TCR of the highly cross-reactive BRLF-1 epitope were noted. BRLF-1 T cell responses were of very high avidity. There was tremendous variation in the Vbeta usage between different individuals and even in the same individual over time. Cross-reactive BRLF-1 responses only became apparent at higher antigen doses in vitro, such as might occur during different phases of infectious mononucleosis.