Maintenance of the EBV-specific CD8<sup>+</sup> TCRab repertoire in immunosuppressed lung transplant recipients — ASN Events

Maintenance of the EBV-specific CD8+ TCRab repertoire in immunosuppressed lung transplant recipients (#133)

Thi H. O. Nguyen 1 2 , Nicola L. Bird 1 2 , Emma J. Grant 1 3 , John J Miles 4 , Paul G. Thomas 5 , Tom C. Kotsimbos 6 7 , Nicole A. Mifsud 6 7 8 , Katherine Kedzierska 1 7
  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia
  2. Authors contributed equally to this work,
  3. Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
  4. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  5. Department of Immunology, St Jude Children’s Research Hospital, Memphis, TN, USA
  6. Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia
  7. These authors also contributed equally to this work,
  8. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia

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, persistence 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 TCRab multiplex-nested RT-PCR to dissect TCRab clonal diversity within GLCTLVAML-specific CD8+ T-cells in healthy individuals and immunocompromised lung transplant recipients. GLCTLVAML (GLC) peptide presented by HLA-A*02:01 is one of the most immunogenic T-cell targets for EBV. We found that the GLC-specific TCRab repertoire was heavily biased towards TRAV5 and encompassed five classes of public TCRabs, 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 TCRab clonotypes/donor. Moreover, pre-transplant GLC-specific TCRab repertoires were relatively stable over 1-year post-transplant under immunosuppression in the absence or presence of EBV reactivation. Additionally, 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 TCRab repertoire after CD8+ T-cell expansion. Our findings provide insights into the stability of EBV-specific TCRab repertoire in immunocompromised transplant patients and suggest that the early detection of EBV-specific T-cells might be a predictor of preceding EBV blood viremia.

  1. Immunol Cell Biol. 2017 95(1):77-86. doi: 10.1038/icb.2016.71.
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