T-cell and B-cell receptor repertoire profiling for biomarker discovery

Abstract

Abstract T-cell receptor (TCR) and B-cell receptor (BCR) repertoire profiling, also referred to as adaptive immune receptor repertoire (AIRR) profiling, holds great potential for the understanding of disease mechanisms and for the development of new treatments in infectious disease, autoimmunity and immuno-oncology. This potential could be greatly improved by combining information about receptor clonotypes with immunophenotypes of T- and B-cells. We developed a new technology for combined profiling of all human TCR and BCR variable regions and phenotypic characterization of immune cells in the same workflow. The TCR and BCR immunophenotyping method involves RT-PCR amplification and sequencing of the CDR3 regions of the TCR and BCR genes, as well as determining the expression levels of the most informative T- and B-cell phenotyping genes. Results show that this method allows for comprehensive profiling of all seven TCR and BCR chains from a single sample, in a highly reproducible manner, directly from micro-samples including cancer tissue, whole blood, sorted cells and more. Bioinformatic analysis of the next-generation sequencing (NGS) data allows profiling of the TCR and BCR clonotypes and identifcation of major immune cell subtypes and their activation status. Preliminary data from rheumatoid arthritis blood samples and others will be presented.