Unlocking the Diagnostic Potential of T Cell Receptors
In humans, cellular immunity is mediated by T cells. T cell receptors (TCRs) are essential to T cell function. The receptors possess a great diversity generated during T cell development sufficient to recognize any peptide, respond to and neutralize the threat. TCRs selectively bind specific antigens as peptides displayed by major histocompatibility complex (MHC) molecules on the surface of antigen presenting cells. Recognition of the peptide–MHC complex occurs on the third hypervariable region termed complementarity determining region 3 (CDR3) on the α and β chains of the TCR causing the T cells to proliferate and mount an immune response. However, the precise information about which antigens are actually recognized has become a critical bottleneck. Presented here is a high throughput analysis pipeline that includes a schema for aligning and characterizing TCR sequences and identifying those TCRs that are specifically expanded by the target antigen; M1 protein. Our findings show that these expanded clones feature recurrent CDR3 β chain amino acid sequences with the same V and J gene usage. Furthermore, the amino acid sequences are derived from different nucleotide sequences indicating that different clones converge on the same recognition site. This reveals the potential to use these TCRs as diagnostic biomarkers. While primarily focused on TCRs that react to well-defined influenza proteins, our approach is applicable to any disease state where T cell immunity is implicated.