VDJdb: a curated database of T-cell receptor sequences with known antigen specificity

Abstract

The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.

Comparative analysis of murine T‐cell receptor repertoires

“…Accumulation and systematization of the knowledge about TCRs with known antigenic specificities (https://vdjdb.cdr3.net/) will allow us to screen analysed repertoires for the presence and abundance of particular antigen‐specific T cells. For example, we have recently applied this approach to track the fate of cytomegalovirus‐ and Epstein–Barr virus‐specific T‐cell clones during human life, from birth to centenarians, revealing expansion of selected clones along with the decrease of antigen‐specific T‐cell diversity.…”

“…Introduction T-cell receptor (TCR) profiling with high-throughput sequencing is becoming an indispensable tool used for studying the adaptive immune response in mouse models and human clinical research. [1][2][3][4] Even before sufficient data, methods and algorithms have been accumulated for massive identification of antigen-specific TCR variants (although efforts are being made [5][6][7][8], rational comparative analysis of the structure of immune receptor repertoires can be highly informative. The informative features of TCR repertoire analysis include, but are not limited to: estimation of repertoire diversity, for which different metrics may be used depending on the questions raised.…”

Systems vaccinology and big data in the vaccine development chain

“…89 For the discovery and analysis of the repertoire of T-and B-cell receptor sequences, VDJviz can be applied for the routine analysis and quality control of sequencing of immune repertoires 90 and VDJdb is designed for the annotation of T-cell receptor repertoire data. 91 These databases evolve and expand continuously based on novel data, scientific insights and technologies. Depending on the choice of data mining tools, the outcome of results might differ.…”

The Bayesian optimist's guide to adaptive immune receptor repertoire analysis

“…86,87 Using these and related tools, recent work has moved toward a variety of machine learning goals, including clustering sequences according to their specificity using tetramer-binding data, 86,88 predicting new sequences that will bind a given epitope, 88 identifying relationships between TCR sequence and MHC use, 80,89 and finding sequences or sequence characteristics that differ between groups. 80,[90][91][92] Building databases of epitope-TCR pairs 93 and high-throughput measurement of affinity 94 will certainly spur this development.…”