The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 134, 751-764, Copyright © 1971 by The Rockefeller University Press


ARTICLE

ANTIBODY-MEDIATED ACTIVATION OF A DEFECTIVE ß-D-GALACTOSIDASE : II. IMMUNOLOGICAL RELATIONSHIP BETWEEN THE NORMAL AND THE DEFECTIVE ENZYME



Franco Celada M.D.1, John Ellis B.S.1, Kerstin Bodlund B.A.1, and Boris Rotman Ph.D.1

1 From the Department of Tumor Biology, Karolinska Institutet, Stockholm, and the Division of Biological and Medical Sciences, Brown University, Providence, Rhode Island 02912

Two closely related protein antigens were used to study immunogenic competition. Namely, normal ß-D-galactosidase of Escherichia coli (Z) and a genetically defective ß-D-galactosidase (AMEF) which seems to differ from the normal in one amino acid substitution. A unique characteristic of this pair of antigens is that, although they are indistinguishable in precipitation and absorption tests with antibodies, the enzymatic activity of AMEF is specifically increased several-hundredfold in the presence of antibodies directed against Z. The following results show that Z and AMEF also differ in their immunogenic ability: (a) antibodies directed against Z activated AMEF; antibodies directed against AMEF did not activate, but competed specifically with activating antibodies. (b) Animals immunized with AMEF failed to produce activating antibodies when they were subsequently challenged with Z, although the presence of some cells primed to produce activating antibodies could be demonstrated by adoptive transfer. (c) Animals preimmunized with Z were stimulated in their production of activating antibodies by AMEF challenge, although not as efficiently as with Z.

A model explaining these observations by competition for the immunogenic site among antigen-sensitive cells carrying cross-reacting receptors is presented.

Submitted on May 24, 1971


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