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T Cell Receptor Profiling in Type 1 Diabetes

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 cell...

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Detalles Bibliográficos
Autores principales: Jacobsen, Laura M., Posgai, Amanda, Seay, Howard R., Haller, Michael J., Brusko, Todd M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636870/
https://www.ncbi.nlm.nih.gov/pubmed/29022222
http://dx.doi.org/10.1007/s11892-017-0946-4
Descripción
Sumario: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.