Innate allorecognition and KIR/lilr/HLA associations in kidney transplantation kidney transplantation is a life-saving treatment for patients with end-stage renal disease

Despite significant improvements in short-term renal allograft survival, long-term graft survival remains suboptimal due to chronic rejection. We hypothesize that innate allorecognition - the sensing of human leukocyte antigen (HLA) in the graft by killer IG-like receptors (KIR) and leukocyte IG-like receptors (lilr) on recipient NK cells and monocytes - is a key driver of chronic rejection. We propose to test the hypothesis by investigating associations between HLA/KIR/lilr genetic variations and clinicopathological allograft outcomes in 2,000 donor/recipient kidney transplant pairs derived from curated north american (pittsburgh and SAN francisco) and french (paris and lyon) patient cohorts that are ethnically diverse. We will perform high coverage short-read and hifi long-read genomic DNA sequencing to obtain high resolution HLA and KIR/lilr typing, respectively. The related KIR and lilr gene families reside adjacent to each other in a region on chromosome 19 that spans