AUTHOR=Peereboom Emma T. M. , Matern Benedict M. , Tomosugi Toshihide , Niemann Matthias , Drylewicz Julia , Joosten Irma , Allebes Wil A. , van der Meer Arnold , Hilbrands Luuk B. , Baas Marije C. , van Reekum Franka E. , Verhaar Marianne C. , Kamburova Elena G. , Seelen Marc A. J. , Sanders Jan Stephan , Hepkema Bouke G. , Lambeck Annechien J. , Bungener Laura B. , Roozendaal Caroline , Tilanus Marcel G. J. , Voorter Christien E. , Wieten Lotte , van Duijnhoven Elly M. , Gelens Mariëlle A. C. J. , Christiaans Maarten H. L. , van Ittersum Frans J. , Nurmohamed Azam , Lardy Neubury M. , Swelsen Wendy , van der Pant Karlijn A. , van der Weerd Neelke C. , ten Berge Ineke J. M. , Bemelman Fréderike J. , de Vries Aiko P. J. , de Fijter Johan W. , Betjes Michiel G. H. , Roelen Dave L. , Claas Frans H. , Otten Henny G. , Heidt Sebastiaan , van Zuilen Arjan D. , Kobayashi Takaaki , Geneugelijk Kirsten , Spierings Eric TITLE=T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.784040 DOI=10.3389/fimmu.2021.784040 ISSN=1664-3224 ABSTRACT=

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.