Category: 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.
Anna Gil– Instructor, University of Massachusetts Medical School
Ramakanth Chirravuri– Student, University of Nebraska Omaha
Larisa Kamga– University of Massachusetts Medical School
Dario Ghersi– Associate Professor, University of Nebraska
Katherine Luzuriaga– Director and PI of the University of Massachusetts Center for Clinical and Translational Science, University of Massachusetts Medical School
Liisa K. Selin– Professor, University of Massachusetts Medical School