{Reference Type}: Journal Article
{Title}: Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.
{Author}: Linsley PS;Nakayama M;Balmas E;Chen J;Barahmand-Pour-Whitman F;Bansal S;Bottorff T;Serti E;Speake C;Pugliese A;Cerosaletti K;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Jun 13
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-48833-w
{Abstract}: 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.