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Genetic and Cellular Factors in the Immune Response

IV. The Effect of Aggregation on Antibody Formation and on Delayed Hypersensitivity in the Inbred ACI and F344 Strains of Rats¹

From the Laboratory of Chemical Pathology, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Abstract

Immunization with an aggregated antigen decreased the antibody response in the highly responding ACI strain and enhanced the antibody response in the poorly responding F344 strain; the effects occurred with a variety of aggregating agents. These findings are consistent with the hypothesis that a major factor in the action of the aggregate is the prolonged retention and slow release of the antigen. There were more differences in the distribution of antibodies among chromatographic subclasses in the F344 strain than in the ACI strain, and these differences did not always correlate with the net charge of the antigen. Most of the differences in the F344 strain were in the antibodies eluting with 0.01 M buffer (IgG₂), whereas the differences in the ACI strain were almost entirely in the antibody eluting with 0.20 M buffer (mainly IgG₁). Aggregating the antigen caused some differences in the chromatographic subclasses of the antibody compared to those elicited by the antigen alone, and the differences were also strain-dependent.

The highly responding ACI strain mounted a strong delayed hypersensitivity response against both free and aggregated poly(Glu⁵²Lys³³Tyr¹⁵), whereas the poorly responding F344 strain was sensitized only by the aggregated polypeptide. Immunization with DNP-poly(Glu⁵²Lys³³Tyr¹⁵) aggregated with MeBSA or with polylysine sensitized the animals to the antigen and the aggregating agent, but not the hapten.

Footnotes

¹ This research was supported by grants from the National Institutes of Health (AI-09520 and GM-1235) and the National Science Foundation (GB-8379).

² Recipient of a Research Career Development Award (K3-CA-5242) from the National Institutes of Health. Present address: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213.