LAUSR

Epstein‐Barr virus (EBV) is one of the most common viruses in humans, capable of causing life‐threatening infections and cancers in immunocompromised individuals. Although CD8+ T cells provide key protection against EBV, the persistence and dynamics of specific T‐cell receptor (TCR) clones during immunosuppression in transplant patients is largely unknown. For the first time, we used a novel single‐cell TCRαβ multiplex‐nested reverse transcriptase PCR to dissect TCRαβ clonal diversity within GLCTLVAML (GLC)‐specific CD8+ T cells in healthy individuals and immunocompromised lung transplant recipients. The GLC peptide presented by HLA‐A*02:01 is one of the most immunogenic T‐cell targets from the EBV proteome. We found that the GLC‐specific TCRαβ repertoire was heavily biased toward TRAV5 and encompassed five classes of public TCRαβs, suggesting that these clonotypes are preferentially utilized following infection. We identified that a common TRAV5 was diversely paired with different TRAJ and TRBV/TRBJ genes, in both immunocompetent and immunocompromised individuals, with an average of 12 different TCRαβ clonotypes/donor. Moreover, pre‐transplant GLC‐specific TCRαβ repertoires were relatively stable over 1 year post transplant under immunosuppression in the absence or presence of EBV reactivation. In addition, we provide the first evidence of early GLC‐specific CD8+ T cells at 87 days post transplant, which preceded clinical EBV detection at 242 days in an EBV‐seronegative patient receiving a lung allograft from an EBV‐seropositive donor. This was associated with a relatively stable TCRαβ repertoire after CD8+ T‐cell expansion. Our findings provide insights into the composition and temporal dynamics of the EBV‐specific TCRαβ repertoire in immunocompromised transplant patients and suggest that the early detection of EBV‐specific T cells might be a predictor of ensuing EBV blood viremia.