Immunity & infection
Acute infectious mononucleosis (AIM) is associated with a massive expansion of CD8+ T-cells which is directed at two HLA-A2:01-restricted EBV epitopes: BMLF1280-288 and BRLF1109-118. During AIM unique cross-reactive CD8+ T-cells between IAV-M1 and EBV-BMLF1 expend and modulate the immune response to EBV correlating with disease severity. Using TCR deep sequencing we showed that EBV-BMLF1 and EBV-BRLF1 TCR-repertoires have a persistent component from AIM to convalescence (CONV), composed of 10% of unique clonotypes, that form 50% of total response, and a non-persistent component, composed of 90% of unique clonotypes, forming 50% of total response, replaced with “de novo” clonotypes in CONV. Here, we postulate that as crossreactive antigen is driving expansion of the IAV-M1 TCR-repertoire during AIM it may follow a similar pattern. TCR deep sequencing ex vivo of cross-reactive IAV-M1 memory from three AIM patients showed that TCR-repertoire differ from healthy donors persistently infected with EBV by using longer CDR3 lengths, highly polyclonal TRAV family with enhanced runs of glycines, and perturbed TRBV-repertoire with reduced use of TCR families, TRAV27 and TRBV19. The IAV-M1 TCR-repertoire mimicked the EBV-specific responses in 2/3 donors with highly individual dominant clonotypes, unusual VA and VB and CDR3 motifs being maintained from AIM to CONV. One donor maintained the CDRb motif “SARD”, a highly public motif found in EBV-BMLF1 T-cell responses. These data would suggest that EBV infection can activate crossreactive influenza A-specific memory cells and influence outcome of infection, but also alter IAV-M1 TCR-repertoire for an extended period of time.