Heavy Chain Variable Region Allotypic Sub-Specificities of Rabbit Immunoglobulins: I. Identification of Three Subpopulations of A1 IgG Molecules¹ Free

Four anti-a1 Ab subpopulations were isolated from an anti-a1 antiserum by sequential immunoadsorption chromatography. These four anti-a1 Ab subpopulations were differentially bound by two “limited heterogeneity” Abs having different components of the a1 allotypic specificity. Each of the four anti-a1 Ab subpopulations reacted with a1 IgG molecules obtained from several different a1 rabbits, but not with IgG obtained from a2 and a3 rabbits. A subpopulation designated anti-a1-A Ab reacted with 100% of a1 IgG molecules. Thus, the anti-a1-A Ab recognizes a1 determinants common to all a1 IgG molecules. Each of the other three subpopulations, designated anti-a1-B Ab, anti-a1-C Ab, and anti-a1-D Ab, and anti-a1-D Ab, reacted with only a fraction of the a1 IgG molecules but the sum of the percentages of a1 IgG molecules which reacted with each of these three anti-a1 Ab subpopulations approximated 100% of the a1 IgG molecules. Thus, each of the anti-a1-B Ab, anti-a1-C Ab, and anti-a1-D Ab recognizes non-common determinants distinct for each of three subpopulations of a1 IgG molecules.

Although 65 to 90% of IgG molecules in a1 homozygous rabbits have the a1 allotypic specificity, these IgG molecules are heterogeneous with respect to their antigenic determinants comprising the a1 allotype; at least three kinds of a1 IgG molecules are identified. This heterogeneity probably reflects variation in the amino acid sequence of the V_H region of a1 IgG molecules and, therefore, poses a similar argument which had led to the hypothesis of two genes for one polypeptide chain and to the theory of episomal insertions for the genetic control of immunoglobulin synthesis.