It is currently thought that the antibody repertoire in the adaptive human immune system evolved to enable it to combat the massive number of foreign antigens derived from pathological bacteria, viruses, toxins, and the like. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent ‘structure and specificity features’, and includes a theoretical model that seems to support it. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens.
There are questions that are relevant at both ends of this number spectrum. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Particularly, we discuss several aspects of challenges in this field and highlight the efforts to develop potential solutions, in the era of high-throughput sequencing of the immune repertoire.īCR High-throughput sequencing Immune repertoire TCR.The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. In this article, we review the history of immune repertoire studies, in terms of technologies and research applications. The massive paralleled sequencing technology suits perfectly the researches on immune repertoire. Before the emergence of high-throughput sequencing, the studies on immune repertoire were limited by the underdeveloped methodologies, since it was impossible to capture the whole picture by the low-throughput tools. Immune repertoire is defined as the sum of T cell receptors and B cell receptors (also named immunoglobulin) that makes the organism's adaptive immune system. The diversity of T and B cells in terms of their receptor sequences is huge in the vertebrate's immune system and provides broad protection against the vast diversity of pathogens.
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