Immunoglobulins with hapten-binding activity: structure-function correlations and genetic implications

✍ Scribed by P. Barstad; J. Hubert; M. Hunkapiller; A. Goetze; J. Schilling; B. Black; Barbara Eaton; J. Richards; M. Weigert; L. Hood

• Book ID: 102826765
• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: English
• Weight: 695 KB
• Volume: 8
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830080709

✦ Synopsis

Abstract

The N‐terminal amino acid sequences of light and heavy chains from mouse myeloma immunoglobulins binding a variety of simple haptens are compared through the first hypervariable region with available sequences from the literature. These comparisons suggest that (a) the heavy chain sequences correlate closely with their respective hapten‐binding specificity, and (b) light chain sequences correlate closely in the case of some specificities (e.g., carbohydrate moieties) but fall into several distinct sets with others (e.g., phosphorylcholine and 2,4‐dinitrophenyl), We suggest that carbohydrate moieties may bind to the antibody combining site by multiple weak noncovalent interactions that require precise complementarity over an extended portion of the combining site. Accordingly, both the light and heavy chains are highly conserved. In contrast, the phosphorylcholine and 2,4‐dinitrophenyl moieties are small and have many possibilities for ionic or charge transfer interactions, but presumably occupy only a small portion of the active site crevice. Hence, a variety of light chain sequences are compatible with active sites that bind these haptens. Even in the case of a small hapten such as phosphorylcholine, however, the light chain sequences place important constraints on the interactions between hapten and immunoglobulin. Heavy/light chain recombination studies reported in this paper reveal the importance of specific heavy/light chain pairing for generation of the antibody specificity to phosphorylcholine. These chain recombination and sequence data also impose important constraints on certain theories of antibody diversity which are discussed.