Swine Xenografts Share Few Predicted Indirectly Recognisable SLA-Derived Epitopes With HLA-Derived Epitopes From Human Kidney Grafts

• Distinct T‑Cell Epitope  Profiles Between Human and Swine Grafts
  Although human leukocyte antigens (HLA) and swine leukocyte antigens (SLA) share significant structural homology, their linear protein sequences differ markedly. Consequently, the sets of peptide fragments (peptidomes) they present—and thus the T‑cell epitopes derived from them—are largely non‑overlapping.

• Minimal Shared T‑Cell Epitopes in Cross‑Species (Human‑Swine) Context
  Using computational modeling via T-memory analysis, the study found a median of only one shared T‑cell epitope between a swine xenograft and a human kidney graft. In contrast, repeat transplants of two human kidneys showed a median of 17 shared T‑cell epitopes. 

• Low Risk of T‑Cell Memory Activation After Xenotransplantation
  The minimal overlap in T‑cell epitopes suggests that swine xenografts likely pose a low risk of inducing memory T‑cell responses that might compromise subsequent human-to-human transplantation. That is, receiving a swine kidney first may not sensitize the recipient’s immune system against a later human.

• Potential Benefit for Highly HLA‑Sensitized Recipients
  The findings point to xenotransplantation as a particularly promising route for individuals who are highly sensitized against HLA (i.e., who have pre-existing anti-HLA immunity). In such patients, swine xenografts could offer a viable alternative with reduced immunological risk.

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