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

• Published in: Frontiers in immunology Vol. 12; p. 784040
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18-11-2021
• Subjects: Adult; Aged; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; graft failure; Graft Rejection - genetics; Graft Rejection - immunology; Graft Survival - immunology; Graft vs Host Disease - diagnosis; Graft vs Host Disease - etiology; Graft vs Host Disease - mortality; HLA antigens; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Immunology; kidney transplantation; Kidney Transplantation - adverse effects; Kidney Transplantation - methods; Male; Middle Aged; PIRCHE-II; Retrospective Studies; shared T-cell epitopes; T-cell epitope; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tissue Donors; Transplant Recipients; Transplantation, Homologous; Treatment Failure; Young Adult; HLA antigens; PIRCHE-II; T-cell epitope; kidney transplantation; T-cell memory; graft failure; shared T-cell epitopes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.784040

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.