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A Nisonoff

Publications and source records attributed to A Nisonoff.

171 records · Page 10Linked to original sources
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Induction of antibodies to pseudorabies virus by immunization with antiidiotypic antibodies.

We have induced the expression of high titres of antibodies to pseudorabies virus (PRV) by immunization of A/J mice with polyclonal antiidiotypic antibodies directed against each of 2 BALB/c monoclonal, neutralizing anti-PRV antibodies. The anti-PRV antibodies induced by one of the antiidiotypic antibody preparations had an affinity for PRV comparable to that of the original monoclonal antibody. Mice immunized with antiidiotypic antibodies were protected to a significant degree against viral infection but the degree of protection was lower than that conferred by passive transfer of monoclonal neutralizing antibody or by immunization with attenuated virus.

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Quantitative assays of idiotype-bearing IgE antibodies.

The present report describes a method allowing quantitation of anti-arsonate IgE antibodies and the estimation of the fraction of such antibodies which expresses the recurring CRIA idiotypic determinant. This method permits an analysis of the regulation of this idiotype within IgE-type antibodies.

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In nature of idiotypes associated with anti-p-azophenylarsonate antibodies in A/J mice.

Antiphenylarsonate (anti-Ar) hybridomas were prepared according to Milstein and Köhler with the cell line 45.6TG1.7 and A/J spleen. About 20% of initial wells with anti-Ar activity expressed the major A/J cross-reactive idiotype. Many wells contained anti-Ar antibodies whose binding to Ar-coated plates was strongly inhibited by antiidiotypic (anti-id) antibody but which did not compete effectively with labelled serum antibody for anti-id. Three such hybridoma products (HP) were cloned twice in agar; a 4th was cloned once. All were IgG1K. Each of the four HP, when specifically purified from a BGG-Ar-Sepharose and then radiolabelled, was strongly bound by anti-id. Pooled purified anti-Ar antibodies and anti-Ar antiserum from 9 of 10 mice competed with each HP for anti-id. The serum of the mouse which was non-inhibitory contained normal amounts of the major cross-reactive idiotype. These results demonstrate the presence of cross-reactive anti-Ar idiotypes other than the major idiotype in the A/J strain. Such idiotypes represent a small proportion of the anti-Ar population. Serological analysis of the four HP, which may reflect the serum antibody population, suggest that these "minor" idiotypes may be quite heterogeneous. An HP which did compete with the major cross-reactive idiotype for anti-id failed to compete with three of the four HP described above. This provides support for the concept that the "minor" idiotypes are serologically distinct from the major cross-reactive idiotype.

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Studies of a cross-reactive idiotype associated with anti-para-azophenylarsonate antibodies of A/J mice.

We have reviewed studies of a cross-reactive idiotype (CRI), associated with anti-para-azophenylarsonate (anti-Ar) antibodies of A/J mice, and have presented some recent data. H chains from molecules with the CRI are homogeneous through the first hypervariable region whereas L chains show heterogeneity in the first framework segment. The constancy of N-terminal H chain sequences from 10 individual mice indicates that the framework is encoded by a germ-line gene, and that mutations have little effect on the observed framework sequence. H chains lacking the CRI show great heterogeneity in the first hypervariable segment, indicating a direct relationship between sequence and idiotype. Adult A/J mice can be suppressed with respect to the production of the CRI by administration of rabbit antiidiotypic antibody. When immunized, such mice produce anti-Ar antibodies with "private" idiotypes present at extremely low concentrations, or absent, in anti-Ar antibodies of other A/J mice. These private idiotypes can be transferred adoptively to mildly irradiated (200 r) syngeneic recipients with lymphoid cells, and serial transfers can be carried out after immunization. The original CRI remains suppressed. This presents the possibility of structural studies of anti-Ar antibodies varying in idiotype from a single strain. The work should also provide information on the degree of diversity of anti-Ar antibodies within the strain.

Amino Acid Sequence↗
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The repertoire of antibodies to a hapten group in an inbred strain of mouse.

We have investigated the diversity of antibodies to the p-azophenylarsonate (Ar) hapten group in the A strain of mouse. The method used consisted of suppressing an idiotype which commonly is observed in the anti-Ar antibodies of all this strain, and then generating anti-idiotypic antisera against the anti-Ar antibodies (lacking the cross-reactive idiotype) which arose after hyperimmunization of the suppressed mice. Anti-idiotypic antibodies prepared against these anti-Ar antibodies were used as a tool to investigate the frequency of recurrence of individual idiotypes in other mice of the same strain. A highly sensitive radioimmunoassay indicated that 3 of the 4 idiotypes studied were virtually undetectable in a panel of 181 A/J mice immunized against the phenylarsonate hapten. A fourth idiotype was found but at very low frequency. The results emphasize the enormous diversity of the immune response to a single hapten group within a strain of mouse. They are interpreted on the basis of hypothesis that the diversity arises through a random series of somatic events. The common cross-reactive idiotype, which is present in the anti-Ar antibodies of all normal A/J mice, is postulated to be the product of a germ-line gene which is closely related to a germ-line gene through a small number of somatic mutations which takes place in every A/J mouse.

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