T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

Emma T.M. Peereboom*, Benedict M. Matern, Toshihide Tomosugi, Matthias Niemann, Julia Drylewicz, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Franka E. van Reekum, Marianne C. Verhaar, Elena G. Kamburova, Marc A.J. Seelen, Jan Stephan Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G.J. TilanusChristien E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Mariëlle A.C.J. Gelens, Maarten H.L. Christiaans, Frans J. van Ittersum, Azam Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. van der Pant, Neelke C. van der Weerd, Ineke J.M. ten Berge, Fréderike J. Bemelman, Aiko P.J. de Vries, Johan W. de Fijter, Michiel G.H. Betjes, Dave L. Roelen, Frans H. Claas, Henny G. Otten, Sebastiaan Heidt, Arjan D. van Zuilen, Takaaki Kobayashi, Kirsten Geneugelijk, Eric Spierings

*Corresponding author for this work

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CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.

Original languageEnglish
Article number784040
JournalFrontiers in Immunology
Publication statusPublished - 18 Nov 2021


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