*Purpose: The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, a member of the B7/CD28 family, triggers an immune checkpoint resulting in inhibition of T cells. Several studies have showed PD-1/PD-L1 single nucleotide polymorphisms (SNPs) affected the molecular structure and function of PD-1. We investigated the impact of SNPs in PD-1/PD-L1 genes on allo-immune responses after clinical kidney transplantation.

*Methods: Ninety-one living donor kidney transplant recipients and their donors were enrolled in this study. Blood samples were obtained from the subjects and genomic DNAs were extracted. By using direct sequencing, PD-1 SNPs, i.e. PD-1.1 (rs36084323), PD-1.3 (rs11568821) and PD-1.9 (rs2227982) were genotyped in the recipients and PD-L1 SNP (rs4143815) was genotyped in the donors. The association between anti-donor T cell responses and PD-1/PD-L1 SNPs were analyzed by using serial immune-monitoring with CFSE-MLR assay after transplantation.

*Results: The recipient’s median age was 49 years (18-73 year), 56 recipients were males and 35 recipients were females. Acute cellular rejection (ACR) occurred in 6 patients, whereas antibody mediated rejection (AMR) occurred in 2 patients. We found no statistical association between either donor PD-L1 or recipients PD-1.3/PD1.9 genotype frequencies and ACR incidence. However, significantly higher incidence of ACR was observed in patients with the PD-1.1 rs36084323 A/G+A/A genotype than in those with the G/G genotype (A carrier vs G/G allele was 8.2 % vs 0 %, p=0.045). The mixed lymphocyte reaction assay performed at 2 and 4 weeks after transplantation showed higher anti‐donor CD4⁺ T‐cell responses in patients carrying rs36084323 A/G+A/A than in those with the G/G genotype (P < 0.05). No significant association was observed between the incidence of AMR and PD-1/PD-L1 SNPs.

*Conclusions: These results suggest that the PD-1 genotype of the recipient plays an important role for the development of ACR after kidney transplantation.

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