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The Effect of Tolerance on the Specificity of the Antibody Response: Antibody to Oxazolonated Albumin of Animals Tolerant to the Protein Carrier¹

From the Subdivision of Immunochemistry, Division of Biological Research, Ontario Cancer Institute, and the Departments of Medical Biophysics and Pathological Chemistry, University of Toronto, Toronto, Ontario, Canada

Abstract

Animals tolerant to human albumin (HA) produce antibody when immunized as adults with oxazolonated derivatives of HA. The proportion of animals producing antibody depends on the number of haptens per molecule of human albumin used in immunization. Two types of antibody-reactivities can be distinguished, one essentially directed to oxazolone and the other directed against protein determinants. The first of these constitutes the larger fraction of the total antibody. The protein antibody appears to be better adapted to the determinants of the native protein than to determinants of the modified protein, and is thus similar to previously described heteroclytic antibodies (18). These antibodies appear to be less well adapted to the immunogen than to a cross-reacting molecule. The findings are discussed in terms of the protein conformation of derivatives and of hypothetical receptor sites through which antibody synthesis may be initiated.

Footnotes

¹ This investigation was supported by The Canadian Arthritis and Rheumatism Society (Grant No. 7-70-(64)); the Medical Research Council (Grant No. MT 832); The National Cancer Institute of Canada; The Ontario Cancer Treatment and Research Foundation (Grant No. 145) and the United States National Institutes of Health (Grant No. 5 T1 GM-506-05). We wish to acknowledge also support of one of us (M. Y.) by a Japanese Imperial Fellowship.

² Present address: The Research Institute of Tuberculosis, Kanazawa University, Kanazawa, Japan.