Amino acid sequences near the “switch point” of heavy chains of human immunoglobulins: Genetic hypothesis

Abstract

We determined amino acid sequences near the juncture between the variable (V-) and the constant (C-) regions of human immunoglobulin (Ig) α, μ, γ1, γ2 and γ3 chains. Our data show that: (a) the γ1, γ2, and γ3 chains are very similar to one another at the beginning of their C-regions with approximately 90% sequence homology and (b) the α chain has more sequence homology with γ chains (57%) than with μ chains (29%) at the beginning of their C-regions, a finding in contrast to the comparison made by others at the C-termini of H-chains where α chain was found to be more homologous to μ than to γ chain. Comparison of our data with amino acid sequences of human γ1 and μ chains published to date shows that: (a) the “switch point” between the V- and C-regions of human Ig H-chains is most likely between positions 117 and 118 (Eu numbering), and (b) several residues at the end of the V-regions are either invariable or nearly invariable. A model is presented as a possible explanation for their significance in the joining of the V-and C-regions.