High-throughput high-accuracy immune repertoire sequencing

Using VDJ recombination, the human immune system contains hundreds of billions of B and T cells that each expresses a unique antigen receptor through a gene recombination mechanism. This “immune repertoire” forms the base of a safety net that protects each individuals against infections and cancers, with particular lymphocytes proliferating in response to antigenic stimulation. Recently developed immune repertoire sequencing technology has enabled us to quantitatively study the immune repertoire in response to vaccination. However, high rate of errors generated from sequencing the PCR amplification process imposed a challenge on accurate determining repertoire diversity and somatic hypermutations. Recently, we developed a RNA barcoding technology that significantly reduced the error rate from 10-3 to 10-5 nt. This new method greatly improved the over-all diversity and mutation estimates and enabled us to answer many questions in human natural infections.