The conserved T cell receptor repertoire observed in patients with systemic lupus erythematosus

The T cell receptor (TCR) is critical for peptide/major histocompatibility (pMHC) recognition and sufficient diversity is required for recognition of the vast array of potential pathogens. Advances in next-generation sequencing technology now permit interrogation of complex sequencing targets at unprecedented depth and reasonable cost. In this study, we used this high-throughput sequencing technology to study the repertoire of TCR beta chains in blood samples collected from a cohort of ten systemic lupus erythematosus (SLE) patients. SLE is a highly complex autoimmune disease, the various forms of which can affect people in different ways. We found that most individual T cell clones were present at very low frequencies, and there were only a small number of sequences that were highly shared among individual. However, the usage frequencies of individual nucleotides, amino acids and TCR beta (TRB)(V/J/D) gene segments within complementarity-determining region (CDR3) intervals were found to be remarkably consistent between individuals. Moreover, our data revealed similar insertion frequencies of individual nucleotides in the V beta-D beta and D beta-J beta junctions among the 10 patients, with terminal deoxynucleotidyl transferase (Tdt) bias towards the insertion of G and C bases over A and T. Overall, our findings indicate the existence of some conserved repertoire features associated with this complex disease. This information may useful in the design of future studies of human TCR gene recombination.