Frontiers in Immunology (Nov 2021)

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,
  • 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. Tilanus,
  • Christien 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,
  • 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

DOI
https://doi.org/10.3389/fimmu.2021.784040
Journal volume & issue
Vol. 12

Abstract

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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.

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