Genetics of Immunoglobulin κ-CHAINS: Chemical Analysis of Normal Human Light Chains of Differing Inv Types

The relationship between Inv phenotype and the amino acid residue at position 191 in κ-type light polypeptide chains derived from the immunoglobulins of ten normal human sera was investigated. In each case, the amino acid present at position 191 correlated with the Inv phenotype of the individual. Kappa chains of seven Inv (—1,3) homozygotes had valine, while those of three Inv (1,3) heterozygotes had some chains with leucine and some with valine at this position. Genes encoding the Inv (1) and Inv (3) variants appear to be expressed equally in the heterozygous state, since approximately equal amounts of each gene product was recovered from heterozygotes. The correlation between Inv phenotype and the amino acid residue present at position 191 is identical to that previously established for κ-type Bence-Jones proteins and myeloma protein light chains. These observations support the hypothesis that the valine-leucine interchange is encoded by two allelic forms of a single κ-chain common region gene.