After RSSs recognition, these enzymes introduce double strand breaks (DSBs), initiating the V(D)J recombination process. Each coding segment is flanked by conserved DNA regions, the recombination signal sequences (RSSs), which serve as cleavage signals for enzymes encoded by recombination activating genes RAG1 and RAG2. The TCR is a heterodimeric plasma membrane protein located on T-cells, and it is composed of two paired chains whose loci are organized as gene segment families comprising a variable (V) gene, a diversity (D) gene, a joining (J) gene and a constant (C) gene.ĭuring T-cell maturation in the thymus, the β and δ chains’ VDJ gene fragments are rearranged as one allele of each gene segment randomly recombines with the others, composing a functional V segment, while, for α and γ chains only, VJ fragments recombine as there is no D gene. The αβ T-cells are essential in cellular immunity since they mediate recognition of antigen peptides in a major histocompatibility complex class I and II (MHC) restricted manner, defining antigen complexes and driving the antigen-specific adaptive immune response against non-self-perceived antigens, including pathogens and cancer neo-antigens, through the TCRs. T-cells, the main actors in cytotoxic immune responses and also contributing to the full activation of the humoral adaptive response, include mainly αβ T-lymphocytes expressing TCR alpha and beta chains and γδ T-cells, a smaller population expressing TCR gamma and delta chains in humans, these different types of T-cells are about 95% and 1–5%, respectively. Īdaptive immunity defense is elicited by large numbers of T-cell receptors (TCRs) and B-cell receptors (BCRs), and perception and adaptation to external insults enhance pre-existing and generate de novo receptors that the immune system records and retains as immunological memory (e.g., with vaccination). The immune system guards multicellular living organisms from the damage of pathogens. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures.
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