*Purpose: Very recently Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) have been suggested to demonstrate early and late effects on kidney allograft outcomes. The association between PIRCHE scoring and donor-reactive T-cells, that have been related to an increased risk of T-cell mediated rejection (TCMR), however, hasn’t been studied and may provide a link for those findings.

*Methods: We analyzed 331 kidney transplant recipients (KTRs) of a first allograft between 2008 and 2015 in our transplant center at Charité Campus Virchow Clinic. KTRs were grouped with respect to preformed donor-reactive T-cells and the development of de-novo donor-reactive T-cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. Donor-reactive T-cells were measured by interferon-γ Elispot assay. HLA epitope mismatches were determined by the PIRCHE approach and PIRCHE scores by recipient HLA class I (PIRCHE-I) and HLA class II (PIRCHE-II) were assessed.

*Results: Among 331 KTRs, 108 KTRs (33%) showed preformed donor-reactive T-cells, and among 223 KTRs without preformed donor-reactive T-cells, 35 KTRs (16%) developed de-novo donor-reactive T-cells. PIRCHE-I and -II scores weren’t associated with the presence of preformed or development of de-novo donor-reactive T-cells (p>0.05). Among 108 KTRs with preformed donor-reactive T-cells, 16 of 40 KTRs (40.0%) with PIRCHE-II score >30 developed TCMR within the first posttranplant year, whereas only 7 of 68 KTRs (10.3%) with PIRCHE-II score <30 developed TCMR (p<0.001). Among 35 KTRs with development of de-novo donor-reactive T-cells, 6 of 13 KTRs (46.2%) with PIRCHE-II score >30 developed TCMR within the first posttranplant year, whereas only 1 of 22 KTRs (4.5%) with PIRCHE-II score <30 developed TCMR (p<0.001). 24 of 188 KTRs (12.8%) without donor-reactive T-cells developed TCMR within the first posttransplant year, that were not associated with PIRCHE-II scores (p=0.587). Among KTRs with donor-reactive T-cells the development of de-novo donor-specific antibodies was independent of PIRCHE-II scores (p=0.409). Among KTRs without donor-reactive T-cells the development of de-novo donor-specific antibodies showed a tendency for higher PIRCHE-II scores (p=0.077).

*Conclusions: PIRCHE didn’t impact the presence of preformed or development of de-novo donor-reactive T-cells. In KTRs with donor-reactive T-cells, PIRCHE-II scores impact the development of TCMR. PIRCHE scores in the absence of donor-reactive T-cells didn’t impact the development of TCMR. The combination of donor-reactive T-cells with PIRCHE scores may allow improved risk stratification with respect to the development of TCMR, whereas PIRCHE scores alone provide limited use.

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