%0 Journal Article
%T Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.
%A Linsley PS
%A Nakayama M
%A Balmas E
%A Chen J
%A Barahmand-Pour-Whitman F
%A Bansal S
%A Bottorff T
%A Serti E
%A Speake C
%A Pugliese A
%A Cerosaletti K
%J Nat Commun
%V 15
%N 1
%D 2024 Jun 13
%M 38871688
%F 17.694
%R 10.1038/s41467-024-48833-w
%X Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas. We identify paired αβ (TRA/TRB) T cell receptors (TCRs) in IAR T cells from the blood of healthy, at-risk, new-onset, and established T1D donors, and measured sequence overlap with TCRs in pancreata from healthy, at risk and T1D organ donors. We report extensive TRA junction sharing between IAR T cells and pancreas-infiltrating T cells (PIT), with perfect-match or single-mismatch TRA junction amino acid sequences comprising ~29% total unique IAR TRA junctions (942/3,264). PIT-matched TRA junctions were largely public and enriched for TRAV41 usage, showing significant nucleotide sequence convergence, increased use of germline-encoded versus non-templated residues in epitope engagement, and a potential for cross-reactivity. Our findings thus link T cells with distinctive germline-like TRA chains in the peripheral blood with T cells in the pancreas.