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Immunol."],"abstract":"<jats:p>CD4<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>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<jats:sup>+<\/jats:sup>memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.<\/jats:p>","DOI":"10.3389\/fimmu.2021.784040","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T08:33:53Z","timestamp":1637224433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation"],"prefix":"10.3389","volume":"12","author":[{"given":"Emma T. 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