Open AccessHuman islet T cells are highly reactive to preproinsulin in type 1 diabetes
Author(s) -
A. Anderson,
Laurie G. Landry,
Aimon A. Alkanani,
Laura Pyle,
Alvin C. Powers,
Mark A. Atkinson,
Clayton E. Mathews,
Bart O. Roep,
Aaron Michels,
Maki Nakayama
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107208118
Subject(s) - cytotoxic t cell , cd8 , islet , type 1 diabetes , proinsulin , biology , antigen , epitope , immunology , pancreatic islets , insulin , endocrinology , diabetes mellitus , medicine , genetics , in vitro
Significance Insulin is a major self-antigen in type 1 diabetes (T1D), and as such, insulin-based immunotherapies have been trialed to treat the underlying autoimmunity but with minimal clinical benefit. Here, we comprehensively assessed reactivity to insulin and its precursor, preproinsulin, by CD8 T cells obtained from the pancreatic islets of organ donors with and without T1D. CD8 T cells highly reactive to peptides throughout the entire preproinsulin protein were only found in T1D donors at varying frequencies. Our results suggest considering the use of preproinsulin rather than just insulin for intervention immunotherapies and have important implications for identifying individuals that may respond to antigen-specific therapies designed to treat autoimmune disorders.