Figure 8. Genetic and structural model for ultralong CDR H3 antibody repertoire formation.

One or more germline V-D-J recombination events using IGHV1-7 (dark purple), IGHD8-2 (dark green), and IGHJ2-4 (dark orange) is shown in the upper left. Junctional diversity, including insertions and deletions, can potentially alter the length of the stalk, as the V-D and D-J joints occur in regions encoding the ascending and descending strands, respectively. Presumably, two disulfide bonds can form in the knob of the naïve/germline antibody (shown in red). The primary repertoire is further diversified in the gut associated lymphoid tissue by AID-mediated processes (upper right). Nucleotide changes that alter amino acid content, particularly to cysteines, can change disulfide patterns and loops (red lines). Larger deletions (black rectangles) in the D_H region can also potentially change loop lengths and disulfide patterns. The β-strands of the knob core and stalk domain are represented by black arrows.