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Structural Studies on Induced Antibodies with Defined Idiotypic Specificities

I. The Heavy Chains of anti-P-Azophenylarsonate Antibodies from A/J Mice Bearing a Cross-Reactive Idiotype¹

From the Department of Microbiology, The University of Texas Southwestern Medical School, Dallas, Texas 75235 and The Department of Biological Chemistry, University of Illinois College of Medicine, Chicago, Illinois 60680

Abstract

Amino acid sequence analysis has been performed on three groups of heavy (H) chains of A/J mice. H chains derived from unimmunized animals were compared to anti-p-azophenylarsonate (anti-Ar) antibodies which were further subdivided into those possessing and those depleted of a cross-reacting idiotype (CRI).

It was found that anti-Ar antibodies bearing the CRI are homogeneous through the first hypervariable region of the H chain. The same sequence was obtained for pooled antibody isolated from the ascites fluid of 18 A/J mice or from a single mouse. The H chains appear to belong to a minor V_H subgroup. In the first 30 positions Anti-Ar antibodies depleted of the CRI had the same sequence as those containing the CRI (with small amounts of heterogeneity at some positions), but contained a mixture of sequences in the first hypervariable region of the H chain.

These studies indicate that antibodies with similar specificity and with identical framework sequences, but which differ in their hypervariable regions, contain different idiotypic determinants, and support the concept that the idiotypic determinants reside primarily within hypervariable regions.

Footnotes

¹ This work was supported in part by grants from the National Science Foundation (GB-41530X) and the National Institutes of Health (AI-12127, AI-06281, and AI-10220).

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