Disulphide shuffling in human IgG2 produces alternative hinge configurations. Disulphide bonds in the hinge and CH1 domains of hIgG2 can rearrange. hIgG2 is thought to be synthesized in its IgG2(A) format where all 4 hinge cysteines are involved in parallel inter-heavy chain disulphide bonds (left). Over time, as it circulates in the blood, these bonds can rearrange and the protein passes through a series of intermediates with a portion achieving a conformation [IgG2(B)] in which both Fab arms are disulphide linked to the hinge. IgG2(A) is thought to have a more open and flexible conformation than the more compact and rigid IgG2(B) (see main text for details and references).