T Cell Receptor Profiling in Type 1 Diabetes

The genetic susceptibility and dominant protection for type 1 diabetes (T1D) associated with human leukocyte antigen (HLA) haplotypes, along with minor risk variants, have long been thought to shape the T cell receptor (TCR) repertoire and eventual phenotype of autoreactive T cells that mediate β-cell destruction. While autoantibodies provide robust markers of disease progression, early studies tracking autoreactive T cells largely failed to achieve clinical utility.

Advances in acquisition of pancreata and islets from T1D organ donors have facilitated studies of T cells isolated from the target tissues. Immunosequencing of TCR α/β-chain complementarity determining regions, along with transcriptional profiling, offers the potential to transform biomarker discovery. Herein, we review recent studies characterizing the autoreactive TCR signature in T1D, emerging technologies, and the challenges and opportunities associated with tracking TCR molecular profiles during the natural history of T1D.