This antigen-driven proliferation process of T cells is distinct between CD4+ and CD8+ T cells after initial antigenic stimulus. When encountering exogenous antigens, T cells that express receptors capable of binding to a specifically compatible peptide–MHC (pMHC) complex will expand, resulting in a massive population of antigen-specific T cells that initiate the adaptive immune response ( 7– 11). ![]() The number of each lymphocyte clone changes dramatically and depends on cell specificity and the history of antigen exposure. The formation and revision of the T and B cell lymphocyte receptor repertoire is a highly dynamic process. This process further diversifies the repertoire and generates BCRs with higher affinity. After encountering cognate antigen, somatic hypermutation introduces point mutations to frame region and complementary determining region of BCRs. In comparison, the light chain (right) is formed only by two segments (V and J), which makes the light chain to be less diverse. Along with the selection of gene segments, insertion and deletion of nucleotides at the junctions between segments provides initial diversity for the primary BCR repertoire. Recombination occurs first between D and J segment, and then V segment and D-J segment. ![]() The structure of each heavy chain (left) originates from rearrangement of Variable (V), Diversity (D), and Joining (J) gene segments. Process of generating a diverse B cell repertoire. We then focus on the success of this technology in facilitating the exploration of infection-related immune repertoires for clinical diagnosis, treatment, and prevention. In this review, we introduce the implementation of HTS to the study of the immune repertoire and review the associated bioinformatic tools required for data processing and analysis. These methods create an unprecedentedly high-resolution picture of the immune repertoire and also provide massive data that cover each lymphocyte from the sample, in theory, dispensing with limitation of sequencing quantity ( 3).Ĭonsidering the extremely important role of the adaptive immune system in defending against infectious agents, HTS has great potential to aid in the discovery novel infectious agents and also offers new approaches for antibody or vaccine development. During the past two decades, however, technical advances in high-throughput sequencing (HTS), also known as next-generation sequencing (NGS), along with evolving bioinformatic and statistical tools, have provided a new approach capable of analyzing the immune repertoire at the single sequence level. However, these low-throughput techniques lack the power to provide a broad picture of the full immune repertoire. ![]() Several sequencing strategies, for example, Sanger sequencing, have been implemented to determine cDNA segments encoding variable regions of immunoglobulin (or TCRs) ( 1, 2). Thus, study of the immune repertoire, portrayed as the antigen-specific information within lymphocytes, has been a key to understanding the response of adaptive immunity during infection.ĭespite extensive efforts using traditional techniques, analysis of the immune repertoire with high resolution has remained difficult. ![]() This profound diversity of T (TCRs) and B cell receptors (BCRs) is generated by V–D–J gene recombination of the TCR/BCR locus and subsequent somatic hypermutation and class-switching recombination of B cells after antigen stimulation. The foundation of the adaptive immune response is based on the enormous diversity of T and B cell antigen receptors that can recognize epitopes from a near infinite number of different internal and external antigens. The adaptive immune system is composed of B and T cells that form a highly selective guard against evolving pathogens.
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