Tracking antigen-specific T cell responses in patients with myocardial infarction

Antigen-specific T cells can impact myocardial diseases, but appropriate model antigens and tools to track specific cells in patients are still lacking. Herein, we sought to identify and functionally characterize specific TCRs recognizing an epitope derived from the human adrenergic receptor beta 1 (ADRB1) presented on HLA-DRB1*13. Peripheral mononuclear cells obtained from HLA-DRB1*13+ subjects were stimulated in vitro with ADRB1167-182 peptide and the expanded CD4+ T cells expressing activation induced markers were sorted for single-cell RNA / TCR-sequencing. Downstream analysis revealed clonal expansion of ADRB1167-182-stimulated CD4+ T cells with a distinct TCR repertoire signature. Moreover, analysis of the TCR{beta} complementarity determining region 3 (CDR3) led to the identification of a distinct motif enriched in ADRB1167-182-stimulated IFN-{gamma}-producing cells. Selected TCRs were expressed in reporter cell lines, and their antigen specificity was further assessed by specific HLA-tetramers and antigen stimulation. Moreover, immunophenotyping of peripheral blood cells from MI patients revealed that ADRB1-specific cells preferentially exhibited a memory phenotype. Taken together, our study provides annotation and functional validation of defined TCRs specific to an antigen relevant to human cardiovascular diseases, offering new tools to track antigen-specific cells in patients with myocardial disease.