Next, as has been observed, nature repeats itself by creating similar clonotypes that appear to have the same function 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and these might be combined into groups. A clonotype can therefore be treated as the minimal functional group of antibodies. All antibodies within a clonotype-a group of antibodies that share a common ancestral recombined cell that arose in a single donor-usually perform the same function. Nevertheless, some inferences can be made. Innovative methods such as mitochondrial lineage tracing could perhaps be used to validate computed clonotypes 26. However, in the absence of a sufficiently large dataset with multiple antigen specificities using cells from multiple humans or donors, it is currently impossible to assess the validity of any functional grouping scheme. In the future, antibody properties might be understood at scale from sequence information alone, perhaps via structural modelling, which could lead to antibody grouping 25. Larger numbers of antibodies can be assayed for simple binding to a particular antigen. In practice, small numbers of antibodies are assayed in vitro–for example, for functional activities such as neutralizing capability. Ideally, antibodies in such groups would share both an epitope and complementary paratopes dictated by their protein sequences. Similar content being viewed by othersĪ central challenge of immunology is the grouping of antibodies by function. For most functional antibodies, the heavy chain determines the light chain. Thus, although naive antibodies seem to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. We also observe this phenomenon when similar heavy chains recur within a donor. This property of functional antibodies is a phenomenon that we call light chain coherence. We show that for naive antibodies (those not yet adapted to antigens), the probability that they use the same light chain V gene is around 10%, whereas for memory (functional) antibodies, it is around 80%, even if only one cell per clonotype is used. Here we consider pairs of B cells that share the same heavy chain V gene and CDRH3 amino acid sequence and were isolated from different donors, also known as public clonotypes 23, 24. ![]() Each chain contains three complementarity-determining regions (CDR1–CDR3), which contribute to antigen specificity. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens 1.
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