title: Maintenance of the EBV-specific CD8+TCRαβ repertoire in immunosuppressed lung transplant recipients.
abstract: 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.
authors: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
authors: Thi Ho
authors: TH
authors: Nguyen
authors: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
authors: Nicola L
authors: NL
authors: Bird
authors: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.|Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors: Emma J
authors: EJ
authors: Grant
authors: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|James Cook University, Cairns, QLD, Australia.
authors: John J
authors: JJ
authors: Miles
authors: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors: Paul G
authors: PG
authors: Thomas
authors: Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia.
authors: Tom C
authors: TC
authors: Kotsimbos
authors: Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
authors: Nicole A
authors: NA
authors: Mifsud
authors: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.
authors: Katherine
authors: K
authors: Kedzierska
mesh_terms: D064591:Allografts / Q000276:immunology; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016040:Lung Transplantation; D010455:Peptides / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D014019:Tissue Donors; D066027:Transplant Recipients; D014775:Virus Activation
chemical_list: D004279:DNA, Viral; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta