The primary structure of a human IgG2 heavy chain: genetic, evolutionary, and functional implications.

Abstract

Abstract The entire amino acid sequence of a human monoclonal immunoglobulin γ2 chain (Til) has been determined. The Til protein represents the second human IgG subclass whose H chain has been completely sequenced. The Til γ2 chain contains 440 amino acid residues—115 in the V region and 325 in the C region. Comparison of this sequence with that of other human and animal γ-chains failed to reveal clear-cut amino acid changes in any of the CH domains that can account for the different biologic effector functions of various IgG subclasses. There is approximately 50 to 75% sequence homology among various mammalian γ-chains within their respective CH domains. The sequence information indicates that the nomenclature for mammalian IgG subclasses does not have any phylogenetic implication. In term of intraspecies comparison, the human y2 chain has approximately 90% or more sequence homology with the human γ1 chain at all three corresponding CH domains. In contrast, the mouse γ1 chain has only 61 to 73% sequence homology with the mouse γ2a chain at the three corresponding CH domains. The guinea pig γ1 chain has 91% sequence homology with its γ2 chains at the chi domain (parallel to that between human γ-chain subclasses) but 70% and 64% homology, respectively, at the corresponding CH2 and CH3 domains (parallel to that between mouse γ-chain subclasses). These comparisons indicate that in man as well as in mouse, exons that encode all three C-region domains of a given γ-chain have evolved in parallel in one germ-line DNA segment as one gene unit, whereas the exons coding for the chi domains of guinea pig γ-chains have evolved independently from those that encode the CH2 and CH3 domains of its y-chains. In guinea pigs, an additional rearrangement of DNA may be necessary for y-chain synthesis, which brings the chi exon from one germ-line DNA segment to the neighborhood of the CH2 and CH3 exons at another noncontiguous germ-line DNA segment during B cell differentiation.