Due to the high number of variants, the sequencing reads will look very different compared to the reference genome and may not be mapped appropriately. These challenges result in existing databases and reference genomes that are neither complete nor accurate (2). The loci are also repetitive in nature and structurally complex. Hypervariable regions such as the TCR gene are incredibly hard to sequence. The massively parallel sequencing of NGS provides the high throughput and quantitative capabilities to examine the immune repertoire at an unprecedented level. High sensitivity is also required to detect the rare clones within the repertoire.
High enough throughput is required to be able to identify all the genetic rearrangements that make up the immune repertoire. Identifying methods to monitor and speed up the recovery of the immune repertoire would also be beneficial.Īccurately determining the immune repertoire is challenging on several fronts. imAEs are also called immune-related adverse events (irAEs) and measuring the immune repertoire may help indicate if a patient will have a greater propensity for them. Immune-mediated adverse events (imAEs) are indeed one of the limiting factors for development of cancer treatments, resulting in patients needing to be nursed back to health in carefully monitored environments. Treatments are also in development to increase the immune repertoire, such as the use of cytokines as drugs.Ī low immune repertoire after therapy, such as cancer treatment, may be a potential side effect of treatment, indicating a weakening of the immune system and resulting greater susceptibility to disease. Measuring the immune repertoire may help to predict therapeutic outcome and be used to monitor the effects of treatment. Numerous treatments are in development and coming into use that affect the immune system. Understanding the immune repertoire is important with the advent of precision medicine and immunotherapy, where treatments are being developed that are tailored to an individual for greater efficacy. In the immune repertoire, only lymphocytes that encounter an antigen with the right receptor to bind to it will be activated and proliferate during an immune response, forming a clone of cells with identical antigen receptors. According to natural selection, organisms that are better suited for an environment thrive and produce offspring. Since T-cell and B-cell lymphocytes are constantly monitoring the body for antigens from foreign bodies, they undergo a process similar to natural selection. At any given point in time, a person’s immune repertoire is made up of ~10 8 lymphocytes with different specificities (1).Įach mature lymphocyte differs from the others in the repertoire in its specificity, and it is ‘clonal’. Researchers also refer to the TCR repertoire and BCR repertoire when studying T cells and B cells, respectively. Immune repertoire refers to all of the unique T-cell receptor (TCR) and B-cell receptor (BCR) genetic rearrangements within the adaptive immune system. Through a mechanism called V(D)J recombination, irreversible somatic DNA recombination of these genetic regions during cellular development results in a mature lymphocyte having a single specificity. This means the adaptive immune system is capable of creating an immunological memory once someone is exposed to an infection, resulting in a more efficient and stronger response to future exposures.Įach unique antigen receptor only recognizes a single antigen and, incredibly, this range of specificity is encoded by a fixed number of gene segments. These lymphocytes have unique antigen receptors acquired through encounters with foreign bodies over a person’s lifetime. The more complex adaptive immune system takes days to respond to an infection and is composed of two major types of lymphocytes called B cells and T cells. The rapid response of your innate immune system also activates the adaptive system, which is the body’s antigen specific response to protect itself. Innate immunity refers to the non-specific defense mechanism that protects the body from a toxin or a foreign object, called an antigen. Your immune system is comprised of two subsystems that work together, providing both innate and adaptive immunity.
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