An amino acid substitution in the γ1 chain of human immunoglobulin g associated with the Gm(2) allotype

Abstract

Thin layer and paper fingerprints of tryptic digests of Fc and pFc' fragments from an IgGl Gm (1,2,17) myeloma protein (Mit) and an IgGl Gm (1,17) myeloma protein were compared to locate differences that might be due to Gm(2). None were found among the 22 peptides that were recovered. Similarly, there were no differences in amino acid content of the 20 peptides whose amino acid content could be determined. However, the octadecapeptide (obtained by cyanogen bromide cleavage) from the Gm (1,2,17) protein had two Gly residues and no Ala residues while previous analyses of Gm(−2), including our own, had shown one of each. The Ala residue is at 431 (Eu numbering). Two heavy chain disease proteins analysed by others showed Gly at 431. We have tested both of these proteins and both are Gm(2). We suggest that Gly at residue 431 is associated with Gm(2) activity. Evidence is presented indicating that some anti-Gm(1) and some anti-Gm(2) antibodies detect two antigenic determinants. One is the allotype, the second is associated with residues between 216 and residues 229 to 236, i.e. essentially the hinge region.