Genetic Bias, Diversity Indices, Physiochemical Properties and CDR3 Motifs Divide Auto-Reactive from Allo-Reactive T-Cell Repertoires

The distinct properties of allo-reactive T-cell repertoires are not well understood. To investigate whether auto-reactive and encoded properties, we used dextramer enumeration, enrichment, single-cell receptor (TCR) sequencing multiparameter analysis. We found T-cells differed in mean ex vivo frequency which was antigen dependent. Allo-reactive showed clear differences TCR architecture, with enriched usage specific variable (TRBJ) genes broader use joining genes. Auto-reactive exhibited complementary determining regions three (CDR3) lengths using a Gaussian distribution whereas distorted patterns CDR3 length. loops from physical-chemical tending to encode that were more acidic charge. diversity metrics, show increased overall homogeneity between repertoires. Motif analysis motif preference included use. Collectively, these data conclude indeed different provide tangible metrics for further investigations validation. Given the antigens studied here overexpressed on multiple cancers TCRs often ligand affinity, this new bank also has translational potential adoptive cell therapy, soluble TCR-based therapy rational design.