AMINO-ACID SEQUENCES OF THE 3 HEAVY-CHAIN CONSTANT REGION DOMAINS OF A HUMAN IGG2 MYELOMA PROTEIN

The amino acid sequences of most of the C(H)1, C(H)2 and C(H)3 domains of IgG Zie, a myeloma protein belonging to the IgG2 subclass, are presented. These data make possible a comparison of the sequences of residues 253-446 of all four subclasses of immunoglobulins; these residues make up almost the entire Fc regions. A comparison can also be made of the G(H)1 domain of IgG1 Eu and the C(H)1 domain of IgG2 Zie. Earlier sequence analyses of the Fc regions of subclass 1 and 3 proteins, 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 show that this very high degree of identity is maintained throughout the four subclasses. Similarly, the C(H)1 domains of γ1 and γ2 chains were found to have 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 immunoglobulin Fc regions, especially since most of the changes are highly conservative. Rather, it seems probable that these functional differences are caused by conformational differences between the subgroups, which result from sequence differences in the hinge regions.