An overview of immunoinformatics approaches and databases linking T cell receptor repertoires to their antigen specificity

Recent advances in molecular and bioinformatic methods have greatly improved our ability to study the formation of an adaptive immune response towards foreign pathogens, self-antigens, and cancer neoantigens. T cell receptors (TCR) are the key players in this process that recognize peptides presented by major histocompatibility complex (MHC). Owing to the huge diversity of both TCR sequence variants and peptides they recognize, accumulation and complex analysis of large amounts of TCR-antigen specificity data is required for understanding the structure and features of adaptive immune responses towards pathogens, vaccines, cancer, as well as autoimmune responses. In the present review, we summarize recent efforts on gathering and interpreting TCR-antigen specificity data and outline the critical role of tighter integration with other immunoinformatics data sources that include epitope MHC restriction, TCR repertoire structure models, and TCR/peptide/MHC structural data. We suggest that such integration can lead to the ability to accurately annotate individual TCR repertoires, efficiently estimate epitope and neoantigen immunogenicity, and ultimately, in silico identify TCRs specific to yet unstudied antigens and predict self-peptides related to autoimmunity.