Simultaneous Recognition of Allogeneic MHC and Cognate Autoantigen by Autoreactive T Cells in Transplant Rejection.

ABSTRACT: The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets. T cells expressing TCRs that are enriched in allograft lesions recognized C3H MHC molecules, and five of six cell lines expressing these TCRs were also reactive to NOD islet c

SUBMITTER: Burrack AL 

PROVIDER: S-EPMC5809255 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature