T-cell Receptor Diversity Estimates for Repertoires (TCRDivER) uses sequence similarity to find signatures of immune response

Abstract

We propose TCRDivER, a global approach to T-cell repertoire comparison using diversity profiles sensitive to both clone size and sequence similarity. As immunotherapies improve, the long standing biological interest in connecting outcome with T cell receptor (TCR) repertoire status has become more urgent. Here we show that new insights can be extracted from high throughput repertoire sequencing data. Most current efforts focus on identification of immunisation-specific sequence motifs or on monitoring changes in frequency of individual clones. Applying TCRDivER to murine spleen samples shows it characterises an additional dimension of repertoire variation, beyond conventional diversity estimates, allowing distinction between immunised and non-immunised samples. We further apply TCRDivER to repertoires from human blood. In both cases we show characteristic relationships between repertoire features. These reveal biologically interpretable relationships between sequence similarity and clonal expansions. We thereby demonstrate a new tool for investigation in clinical and research applications.