However, the underlying mechanism by which these repertoires are ontogenetically developed and shaped is largely unknown. It is well-characterized that such huge diversity of antigen-specific receptors is created through somatic rearrangement of variable (V), diversity (D), and joining (J) (or V and J) gene segments located in TCR- or BCR/Ig-encoding loci and the concomitant incorporation of random nucleotide insertions and deletions. At the individual level, the estimated number of TCR and BCR/Ig clonotypes is from a few thousands to more than billions depending on the species of animal, which is believed to form the basis of the host ability to cope with innumerable immunologic threats. At the single-cell level, these cells express a single type of unique antigen-specific receptors: T-cell receptor (TCR) for T cells and B-cell receptor/immunoglobulin (BCR/Ig) for B cells that define a phenotypic clone or a clonotype of these immune cells. In this paradigm of the “adaptive” immune system, it is firmly believed that pre-existing repertoire of two types of lymphohematopoietic cells, classic T cells and B cells, predominantly determine the mode and pattern of immune responses in a given individual. The jawed vertebrates have evolutionally acquired a unique immune system consisted of effector and regulator cells that can effectively respond or establish tolerance to millions of endoneous and environmental antigens in an epitope-specific manner ( 1). Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host–microbiome immune homeostasis. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. 4Department of Rheumatology and Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, National Hospital Organization Sagamihara Hospital, Sagamihara, Japan.2Repertoire Genesis Incorporation, Ibaraki, Japan.1Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Hiroshima, Japan.These autoimmune diseases can exhibit slightly or significantly skewed IRs and provide novel insights that inform our comprehending of disease pathogenesis and provide potential targets for diagnosis and treatment.īCR Immune repertoire SLE TCR autoimmune diseases. In this review, we summarize updated progress on the mechanisms of the IR and current related studies on four autoimmune diseases, particularly focusing on systemic lupus erythematosus (SLE). In the field of IR, HTS can monitor the immune response status and identify disease-specific immune repertoires. Rapid advancements in high-throughput sequencing (HTS) technology have ushered in a new era of immune studies, revealing novel molecules and pathways that might result in autoimmunity. At the same time, bias or abnormalities in the IR also pay a contribution to the pathogenesis of autoimmune diseases. The diversity of the immune repertoire (IR) enables the human immune system to distinguish multifarious antigens (Ags) that humans may encounter throughout life.
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