![]() AIRR sequencing (AIRR-seq) provides insights into the immune status of an individual at steady-state or in altered conditions such as malignancy, autoimmune disease, immunodeficiency, infectious disease, or vaccination, and allows comparison of B- and T-cell populations between individuals and time points ( Benichou et al., 2012 Kirsch et al., 2015 Dziubianau et al., 2013 Hou et al., 2016 Ghraichy et al., 2018). Thanks to next-generation sequencing (NGS), the AIRR can be sampled with sufficient depth for some of its complexity to be studied ( Weinstein et al., 2009 Six et al., 2013). ![]() The adaptive immune repertoire is very diverse in a healthy individual, with the theoretically possible number of clonotypes reaching more than 10 19 different TR ( Bradley and Thomas, 2019) and 10 11 IG ( Glanville et al., 2009), far exceeds the number of B and T cells in a given individual ( Davis and Bjorkman, 1988 Freeman et al., 2009 Elhanati et al., 2015). ![]() The total number of potential expressed rearranged IG and TR sequences in an individual is referred to as the adaptive immune receptor repertoire (AIRR). The diversity of the resulting rearranged genes (referred as V-J and V-D-J) is very high, due to not only the combination of different germline V, D, and J genes, but also to the deletion and addition of templated (P) nucleotides and the addition of non-templated (N) nucleotides at the junctions between the rearranged genes, and somatic hypermutation of expressed IG ( Papavasiliou and Schatz, 2002 Lefranc and Lefranc, 2020). Immunoglobulin chains (IG) and T-cell receptor chains (TR) are generated by DNA recombination, a process of somatic rearrangement of variable (V), diversity (D), and joining (J) genes ( Tonegawa, 1983).
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