![]() Multiple contiguous variable gene segments (TCRV) are present at each immune globulin locus. How does the adaptive immune system generate antigen receptors with such a huge diversity to cover recognition of a plethora of antigens? The answer is that complete genes that encode a variable region are generated by the somatic recombination of separate gene segments. The effectiveness of the adaptive immune system strongly depends on the diversity and availability of antigen receptors. Thus, high-throughput sequencing has enabled the profiling of TCRs and BCRs in single cells and of transcriptomes at an impeccable resolution, which is greatly adding to our understanding of adaptive immune responses in health and disease. In particular, single-cell sequencing made it possible to determine the relationship and dynamics of antibody and TCR repertoires with more accuracy on the single-cell level. They facilitated the parallel analysis of millions of TCR and BCR (B cell receptor) sequences. ĭespite many ingenious methods, technical limitations have made it difficult for many years to create a comprehensive overview of TCR repertoires, until highly specific methods based on next-generation sequencing were developed. Correlation of antigen-specific T cells with their respective functional polarization and differentiation state provides further qualitative measures of protection and tolerance. It represents a reflection of the individual’s history of antigen exposures. All individual TCRs of a given individual comprise the TCR repertoire. They can therefore serve as biomarkers of host protection. Some of them will persist after a contraction phase to provide long-term immunological memory, i.e., against viral antigens. Clonally expanded T cells express the same unique TCR. Quantitative shifts in T cells with distinct T-cell receptors occur as a result of proliferation and thus clonal expansion in response to cognate antigens, which can originate from a plethora of microbial pathogens but also autoantigens. Long-lasting T- and B-cell responses are the hallmark of immunological memory. In order to help immunologists to choose from the vastness of available tools for their data analysis, this review addresses and compares commonly used bioinformatics tools for TCR repertoire analysis and illustrates the advantages and limitations of these tools from an immunologist’s perspective. Thus, researchers are now confronted with the issue of having to choose the right kind of approach to analyze, visualize and ultimately solve their task at hand. Many different tools and methods, specifically designed for various aspects of immunological research, have recently emerged. This requires a suite of highly sophisticated bioinformatics tools to leverage the meaning and complexity of the large datasets. Their interrogation yields large amounts of data. They serve as correlates of host protection and tolerance, as well as biomarkers of immunological perturbation by natural infections, vaccines or immunotherapies. T-cell receptor (TCR) repertoires carry comprehensive information on the history of an individual’s antigen exposure. The development of next-generation sequencing (NGS) and single-cell technologies also brought forth a revolution in the characterization of immune repertoires. Particularly the field of immunology has seen great strides in recent years. ![]() Over the last few years, there has been a rapid expansion in the application of information technology to biological data. ![]()
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