Maintenance of the EBV-specific CD8+ TCRαβ repertoire in immunosuppressed lung transplant recipients
Nguyen, Thi H.O., Bird, Nicola L., Grant, Emma J., Miles, John J., Thomas, Paul G., Kotsimbos, Tom C., Mifsud, Nicole A., and Kedzierska, Katherine (2016) Maintenance of the EBV-specific CD8+ TCRαβ repertoire in immunosuppressed lung transplant recipients. Immunology and Cell Biology, 95. pp. 77-86.
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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, 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 TCRαβ multiplex-nested RT-PCR to dissect TCRαβ 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 TCRαβ repertoire was heavily biased towards 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. 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 TCRαβ repertoire after CD8+ T-cell expansion. Our findings provide insights into the stability of EBV-specific TCRαβ 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.
| Item ID: | 45623 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1440-1711 |
| Additional Information: | This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Funders: | National Health and Medical Research Council (NHMRC) |
| Projects and Grants: | NHMRC ID1071916 and ID 1102792 |
| Date Deposited: | 13 Sep 2016 21:53 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320402 Applied immunology (incl. antibody engineering, xenotransplantation and t-cell therapies) @ 100% |
| SEO Codes: | 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100% |
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