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Immune repertoire6/13/2023 When the end-point of such activities is examined, the number of observable circulating antibodies is typically a much smaller number, in the 1,000’s, as is the number of observable T-cell receptors. T-cell receptor genes have a similar set of C, V, D and J gene segments that can undergo rearrangement in a similar way to generate a library of T-cell receptors (1), (7). DNA rearrangement allows the generation of roughly 3×10 11 combinations, one per B-cell, although some are removed due to self-reactivity. The light chains also possess a similar set of C, V and J segments but are lacking in D. The human immunoglobulin heavy chain region contains 2 constant (C) and 44 variable (V) gene segments, as well as 27 diversity (D) and 6 joining (J) gene segments. Heavy and light chain genes contain multiple copies of three different types of gene segments which define the variable (CDR) regions of antibodies. The answer was what is now known as V(D)J recombination (7), the underlying genetic principle by which antibody diversity is generated and for which Susumu Tonegawa was awarded the Nobel Prize in Physiology or Medicine in 1987 (8). An interesting aside here is that this belief or dogma should not be confused with the “Central Dogma of Molecular Biology”, a lasting example of poor choice of English by an esteemed British researcher, Francis Crick (6). This was a particularly daunting question to answer since, at the time, researchers believed that DNA sequences were fixed and struggled to envision how they could be changed or modified to produce a potentially large array of an estimated maximum of 10 11 variants of immunoglobulin and 10 11 T-cell receptor sequences. Some years ago a major question in the world of immunology was how the immune system generated a large repertoire of both immunoglobulins from the B-cells and T-cell receptors on the T-cells where the receptor is the topological equivalent to an antigen-binding fragment of the antibody (5). There are two key components of the immune repertoire: the immunoglobulins (AKA antibodies), constructed from two B-cell derived proteins, the so called heavy and light chains and the T cell receptors constructed from four T-cell derived proteins, labeled alpha, beta, gamma and delta, although only alpha and beta actually vary (4). The adaptive component (3), which has a relatively long response time and is usually referred to as the immune repertoire, is produced by B-cells and T-cells to help with the recognition and response to various external insults such as viruses, bacteria, worms, parasites and related micro-organisms, unwelcome chemicals and toxins, as well as modified “self” cells such as cancerous cells. The innate component, often thought of as hereditary, consists of a complex mix of anatomical barriers to pathogens as well as cellular responses and is typically ready for immediate action (2). The immune systems within most vertebrates have both an innate component and an adaptive component (1).
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