STRUCTURAL STUDIES OF GAMMA HEAVY CHAIN DISEASE PROTEINS

Studies of the structure of heavy chain disease (HCD) proteins may be informative concerning the genetic mechanisms utilized in the synthesis of normal immunoglobulins. This paper will present and discuss information on two previously unreported cases of y-HCD. y-HCD was isolated from the urine of Rip and the pleural fiuid of 0. A.1 by precipitation with ammonium sulfate, anion exchange chromatography and gel filtration on Sephadex G-200. Some of the characteristics of these two proteins are compared with those of four other proteins that have been studied in our laboratory (TABLE 1). Heavy chain subclasses of 0. A., Rip and Hin could not be directly established, since they did not precipitate with any of the antisera defining the four subclasses of IgG. Both 0. A. and Rip were of the IgGl subclass, since they carried the genetic marker G m l which is restricted to G I proteins. (The authors are grateful to Dr. Arthur Steinberg for determining Gm factors.) Both proteins consisted of disulfide-linked polymers, since apparent molecular weight, as determined by rate of electrophoretic migration in 10% acrylamide gel containing 0.1 % SDS, was higher in unreduced than in reduced samples. Approximate monomer molecular weights, shown in the last column of TABLE 1, were determined by acrylamide gel electrophoresis with appropriate marker proteins of known molecular weight.6 The only protein studied to date that apparently does not contain disulfide-linked polymers is Hin and, as reported e l~ewhere ,~