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

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


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
Number of pages13
JournalFrontiers in Immunology
Publication statusPublished - 18 Nov 2021


  • HLA antigens
  • graft failure
  • kidney transplantation
  • shared T-cell epitopes
  • T-cell epitope
  • T-cell memory
  • HELP

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