The amino acid sequences of the three heavy chain constant region domains of a human IgG2 myeloma protein

Abstract

The amino acid sequences of most of the CH[H chain constant region]1, CH2 and CH3 domains of Ig[immunoglobulin]G Zie, a myeloma protein belonging to the IgG2 subclass were presented. These data make possible a comparison of the sequences of residues 253-446 of all 4 subclasses of Ig; these residues make up almost the entire Fc regions. A comparison can also be made of the CH1 domain of IgG1 Eu and the CH1 domain of IgG2 Zie. Earlier sequence analyses of the Fc regions of subclass 1 and 3 protiens, and parts of the Fc regions of subclass 2 and 4 proteins showed that about 95% of these sequences were identical. The extended comparisons made possible by the data presented here showed that this very high degree of identity was maintained throughout the four subclasses. Similarly, the CH1 domains of .gamma.1 and .gamma.2 chains had about 93% sequence identity. It is unlikely that the few single amino acid changes within the constant region domains can account for the marked differences between subclasses observed in the biological effector functions of Ig Fc regions, espceially since most changes are highly conservative. These functional differences are probably caused by conformational differences between the subgroups, which result from sequence differences in the hinge regions.