TY - JOUR
T1 - T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation
AU - Peereboom, Emma T M
AU - Matern, Benedict M
AU - Tomosugi, Toshihide
AU - Niemann, Matthias
AU - Drylewicz, Julia
AU - Joosten, Irma
AU - Allebes, Wil A
AU - van der Meer, Arnold
AU - Hilbrands, Luuk B
AU - Baas, Marije C
AU - van Reekum, Franka E
AU - Verhaar, Marianne C
AU - Kamburova, Elena G
AU - Seelen, Marc A J
AU - Sanders, Jan Stephan
AU - Hepkema, Bouke G
AU - Lambeck, Annechien J
AU - Bungener, Laura B
AU - Roozendaal, Caroline
AU - Tilanus, Marcel G J
AU - Voorter, Christien E
AU - Wieten, Lotte
AU - van Duijnhoven, Elly M
AU - Gelens, Mariëlle A C J
AU - Christiaans, Maarten H L
AU - van Ittersum, Frans J
AU - Nurmohamed, Azam
AU - Lardy, Neubury M
AU - Swelsen, Wendy
AU - van der Pant, Karlijn A
AU - van der Weerd, Neelke C
AU - Ten Berge, Ineke J M
AU - Bemelman, Fréderike J
AU - de Vries, Aiko P J
AU - de Fijter, Johan W
AU - Betjes, Michiel G H
AU - Roelen, Dave L
AU - Claas, Frans H
AU - Otten, Henny G
AU - Heidt, Sebastiaan
AU - van Zuilen, Arjan D
AU - Kobayashi, Takaaki
AU - Geneugelijk, Kirsten
AU - Spierings, Eric
N1 - .
PY - 2021/11/18
Y1 - 2021/11/18
N2 - 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.
AB - 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.
KW - HLA antigens
KW - PIRCHE-II
KW - graft failure
KW - kidney transplantation
KW - shared T-cell epitopes
KW - T-cell epitope
KW - T-cell memory
KW - ANTIBODY-MEDIATED REJECTION
KW - INDIRECT RECOGNITION
KW - CROSS-VALIDATION
KW - DR PEPTIDES
KW - ANTIGEN
KW - LYMPHOCYTES
KW - ALLOCATION
KW - MEMORY
KW - ASSAY
KW - HELP
U2 - 10.3389/fimmu.2021.784040
DO - 10.3389/fimmu.2021.784040
M3 - Article
C2 - 34868064
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 784040
ER -