The human T-cell receptor repertoire in health and disease and potential for omics integration

The adaptive immune system arose 600 million years ago in a cold-blooded fish. Over countless generations, our antecedents tuned the function of the T-cell receptor (TCR). The TCR system is arguably the most complex known to science. The TCR evolved hypervariability to fight the hypervariability of pathogens and cancers that look to consume our resources. This review describes the genetics and architecture of the human TCR and highlights surprising new discoveries over the past years that have disproved very old dogmas. The standardization of TCR sequencing data is discussed in preparation for big data bioinformatics and predictive analysis. We next catalogue new signatures and phenomenon discovered by TCR next generation sequencing (NGS) in health and disease and work that remain to be done in this space. Finally, we discuss how TCR NGS can add to immunodiagnostics and integrate with other omics platforms for both a deeper understanding of TCR biology and its use in the clinical setting.

Automated summary

The TCR system, believed to be one of the most complex in science, evolved over 600 million years and has been fine-tuned by generations of our ancestors. Recent discoveries have challenged old dogmas in the field, shedding new light on TCR biology. Standardizing TCR sequencing data is crucial for big data bioinformatics and predictive analysis, while TCR NGS has the potential to uncover new signatures and phenomena in health and disease.