IgG is the predominant immunoglobulin in the serum and has a molecular weight of about 150 kDa. Four distinct subgroups of human IgG (IgG1, IgG2, IgG3, and IgG4) were first demonstrated in the 1960’s by using polyclonal antisera prepared in animals immunized with human myeloma proteins. Quantitatively, the relative serum concentrations of the IgG subclasses are as follows: IgG1 > IgG2 > IgG3 = IgG4. The four IgG subclasses show their most conspicuous differences in the amino acid composition and structure of the 'hinge region', which is the part of the molecule containing disulfide bonds between the y-heavy chains. The hinge region of IgG1 encompasses amino acids 216-231 and since it is freely flexible, the Fab fragments can rotate about their axes of symmetry and move within a sphere centered at the first of two inter-heavy chain disulfide bridges.