Immune Response to Substituted Arsanilazo–Human Gamma Globulin Conjugates in Mice Tolerant to Human Gamma Globulin

Abstract

I HAVE recently investigated the immune response to a variety of azo–human gamma globulin derivatives in mice tolerant to the carrier protein, human gamma globulin (HGG)¹. Judged by the elimination of trace-labelled HGG, it seemed that a single injection of azo-protein in Freund incomplete adjuvant had only a marginal effect on tolerance. Two exceptions were noticed, however, in experiments where mice tolerant to HGG wrere challenged with either double substituted azo–HGG or with o-sulph-anil-azo–HGG. On the other hand, compared with controls challenged with HGG, two injections of azo–HGG, 4–5 weeks apart, usually caused a significant increase in the number of responsive mice. Gel-diffusion techniques revealed that the injection of azo-proteins did not regularly cause a full return to responsiveness to HGG in mice neonatally rendered tolerant to this protein. The specificity of the antibody formed was found to be directed against antigenic determinants comprising the haptenic group and part of the protein carrier. The altered HGG preparations used had 2.6–13.6 azo groups per molecule of HGG and cross-reacted to 80–100 per cent with native HGG. The following experiments were devised to investigate the effect of azo–HGG with more haptenic groups attached and cross-reacting to a lower extent than the preparations previously used.