Advanced Methodologies in High-Throughput Sequencing of Immune Repertoires

In recent years, major efforts have been made to develop sophisticated experimental and bioinformatic workflows for sequencing adaptive immune repertoires. The immunological insight gained has been applied to fields as varied as lymphocyte biology, immunodiagnostics, vaccines, cancer immunotherapy, and antibody engineering. In this review, we provide a detailed overview of these advanced methodologies, focusing specifically on strategies to reduce sequencing errors and bias and to achieve high-throughput pairing of variable regions (e.g., heavy-light or alpha-beta chains). In addition, we highlight recent technologies for single-cell transcriptome sequencing that can be integrated with immune repertoires. Finally, we provide a perspective on advanced immune repertoire sequencing and its ability to impact basic immunology, biopharmaceutical drug discovery and development, and cancer immunotherapy.