T Cell Receptor Profiling in Type 1 Diabetes

Abstract

Purpose of Review: 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. Recent Findings: 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. Summary: 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.