Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Temporal development of T cell receptor repertoires during childhood in health and disease
Angela M. Mitchell, … , Maki Nakayama, Aaron W. Michels
Angela M. Mitchell, … , Maki Nakayama, Aaron W. Michels
Published August 23, 2022
Citation Information: JCI Insight. 2022;7(18):e161885. https://doi.org/10.1172/jci.insight.161885.
View: Text | PDF
Research Article Immunology

Temporal development of T cell receptor repertoires during childhood in health and disease

  • Text
  • PDF
Abstract

T cell receptor (TCR) sequences are exceptionally diverse and can now be comprehensively measured with next-generation sequencing technologies. However, a thorough investigation of longitudinal TCR repertoires throughout childhood in health and during development of a common childhood disease, type 1 diabetes (T1D), has not been undertaken. Here, we deep sequenced the TCR-β chain repertoires from longitudinal peripheral blood DNA samples at 4 time points beginning early in life (median age of 1.4 years) from children who progressed to T1D (n = 29) and age/sex-matched islet autoantibody-negative controls (n = 25). From 53 million TCR-β sequences, we show that the repertoire is extraordinarily diverse early in life and narrows with age independently of disease. We demonstrate the ability to identify specific TCR sequences, including those known to recognize influenza A and, separately, those specific for insulin and its precursor, preproinsulin. Insulin-reactive TCR-β sequences were more common and frequent in number as the disease progressed in those who developed T1D compared with genetically at risk nondiabetic children, and this was not the case for influenza-reactive sequences. As an independent validation, we sequenced and analyzed TCR-β repertoires from a cohort of new-onset T1D patients (n = 143), identifying the same preproinsulin-reactive TCRs. These results demonstrate an enrichment of preproinsulin-reactive TCR sequences during the progression to T1D, highlighting the importance of using disease-relevant TCR sequences as powerful biomarkers in autoimmune disorders.

Authors

Angela M. Mitchell, Erin E. Baschal, Kristen A. McDaniel, Kimber M. Simmons, Laura Pyle, Kathleen Waugh, Andrea K. Steck, Liping Yu, Peter A. Gottlieb, Marian J. Rewers, Maki Nakayama, Aaron W. Michels

×

Graphical abstract

Options: View larger image (or click on image)

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts