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A Nisonoff

Publications and source records attributed to A Nisonoff.

At least 55 records · Page 3Linked to original sources
PubMed1984

Independent regulation of serologically distinct idiotypes in F1 hybrid mice.

We have investigated the regulation of expression of two distinct intrastrain cross-reactive idiotypes, CRIA and CRIC , characteristic of anti-p-azophenylarsonate (anti-Ar) antibodies of the A/J and BALB/c strains, respectively, in (BALB/c X A/J)F1 ( CAF1 ) mice. Such hybrid mice were found to synthesize antibodies with each idiotype when immunized against the Ar hapten group, although the expression of each was significantly reduced as compared with the parental strain. CAF1 mice were pretreated with idiotypic-specific antibody reagents and subsequently hyperimmunized against the Ar hapten. Analysis of the idiotypes present in immune sera showed that suppression of either CRI did not concomitantly suppress the expression of the other. Alteration of the expression of one idiotype was not, however, without influence on the other; the expression of CRIC was markedly enhanced in mice suppressed for CRIA.

Animals↗
PubMed1983

Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses.

Two different cross-reactive idiotype (CRI) groups are distinguishable in the Ab response of A/J mice to the p-azobenzenearsonate (ABA) hapten: CRIA and CRIm. These two groups showed distinct patterns of relative dominance in the ensuing response depending on whether the inducing Ag was a T cell-dependent (TD) form of ABA, such as ABA-KLH or ABA-CGG, or a T-independent type 1 (TI-1) form, such as ABA-Brucella abortus or ABA-lipopolysaccharide (LPS), and on whether the response was elicited in vivo or in vitro. The CRI+ component of primary in vivo plaque-forming cell (PFC) responses to TD ABA Ags was largely (greater than 90%) CRIA+ as was, to a slightly lesser extent (greater than 75%) the CRI+ portion of secondary or hyperimmune serum Ab or PFC responses to the same Ags. In contrast, in vivo primary and hyperimmune PFC responses to ABA-Bru or ABA-LPS showed a significantly lower CRIA/CRI ratio, averaging 0.5-0.6, with some individual mice giving figures as low as 0.2, indicating predominance of CRIm over CRIA. Serological analysis of hyperimmune anti-ABA Abs from a group of 5 A/J mice immunized with ABA-Bru gave a figure of less than 0.5 for the CRIA/CRI ratio. The most striking disparity from the TD pattern was seen in primary in vitro PFC responses to the TI ABA Ags; here ratios of less than 0.2 were generally seen. Since T cell removal did not alter the Id pattern in the TI responses, CRIA-specific Ts cells do not account for the weak expression of CRIA in such responses. We propose a model that explains these results on the basis of differential expression of IdX dominance by two distinct B cell subpopulations--equatable to the Lyb-5+ and Lyb-5- B cell subsets--along with differential relative activation of these subsets in different types of responses. Examination of anti-ABA PFC responses of F1 progeny of CBA/N and A/J mice to ABA-Bru lends support to this hypothesis since CRIA expression was significantly lower in mice with the xid defect.

Animals↗
PubMed1983

Preliminary crystallographic study of the Fab fragment of a monoclonal anti-phenylarsonate antibody.

Preliminary crystallographic data are given for the Fab fragment of a monoclonal anti-p-phenylarsonate antibody. This crystalline Fab fragment was found by screening a number of monoclonal anti-arsonate antibodies obtained from hybrids of A/J immune spleen cells with a non-secreting mouse myeloma line. The protein crystallizes in the monoclinic space group P21 with a = 86.2 +/- 0.1 A, b = 80.4 +/- 0.2 A, c = 75.8 +/- 0.1 A, beta = 90.3 +/- 0.1 degrees. Precession photographs show X-ray reflections extending to a resolution of 3 A.

Antibodies, Monoclonal↗
PubMed1983

Preparation of F(ab')2 fragments from mouse IgG of various subclasses.

We have investigated the effects of peptic digestion on mouse monoclonal immunoglobulins of each subclass of IgG. F(ab')2 fragments were obtained in good yield from IgG1, IgG2a and IgG3 proteins. The relative rates of digestion were IgG3 greater than IgG2a greater than IgG1. Variations in rate of digestion were noted for individual monoclonal IgG3 proteins. Five different IgG2b proteins were degraded very rapidly without the detectable formation of antigen-binding F(ab')2 fragments. One IgG1 protein out of four tested was also rapidly degraded.

Animals↗
PubMed1983

Passive transfer of the idiotypically suppressed state by serum from suppressed mice and transfer of suppression from mothers to offspring.

Mice that are suppressed with respect to an idiotype (CRIA) present in A/J anti-p-azophenylarsonate antibodies, hyperimmunized, and allowed to rest were previously found to possess high concentrations of suppressor T cells with anti-idiotypic receptors. We have now observed that the sera of such mice contain soluble factors that can selectively suppress the CRIA component of a humoral response when passively transferred to adult or neonatal recipients. When T cells from suppressed, hyperimmunized mice were transferred into female mice before mating, their offspring, upon immunization, produced anti-Ar antibodies that lacked CRIA. A state of idiotypic suppression was also produced in offspring when the mother was inoculated with serum from suppressed mice a few days before parturition. The results indicate that the suppressor factor is not an immunoglobulin.

Animals↗
PubMed1983

Adoptive transfer of resistance to growth of an idiotype-secreting hybridoma by T cells from idiotypically suppressed mice.

A/J or CAF1 mice that are suppressed with respect to an idiotype, CRIA, associated with anti-Ar antibodies, and hyperimmunized develop high concentrations of idiotype-suppressor T cells. In this paper we show that such CAF1 mice are resistant to the growth of a CRIA-positive hybridoma that is lethal in normal or in immunized non-suppressed mice. No resistance was observed to the growth of a hybridoma secreting anti-Ar antibodies that lack CRIA. The state of resistance could be adoptively transferred to naive syngeneic recipients with spleen cells or T-enriched spleen cells from suppressed hyper-immunized mice; B-enriched cells were ineffective.

Animals↗
PubMed1983

Presence of an intrastrain cross-reactive idiotype on A/J antibodies of the IgE class specific for the p-azophenylarsonate group.

An intrastrain cross-reactive idiotype, CRIA, is associated with a large proportion of the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. The present experiments, in which the methods of direct and reverse passive cutaneous anaphylaxis (RPCA) were used, indicate that IgE anti-Ar antibodies are produced in A/J mice upon stimulation with a protein-Ar conjugate and that a large proportion of these antibodies express CRIA. The use of monoclonal anti-CRIA for RPCA eliminated the strong nonspecific reactions previously observed. The results provide a basis for studying factors that regulate the switch to IgE biosynthesis during an immune response.

Animals↗
PubMed1982

Content of a cross-reactive idiotype in nonimmune A/J sera.

The anti-p-azophenylarsonate antibodies of A/J mice express a major intrastrain cross-reactive idiotype (CRIA). Using a sensitive radioimmunoassay we were unable to detect significant quantities of molecules bearing CRIA in nonimmune A/J sera. The upper limit is 140 ng/ml. Possible reasons for variability of such data in the published literature are discussed.

Animals↗
PubMed1982

Degree of heterogeneity of binding specificities of antibodies to the phenylarsonate group that share a common idiotype.

We have investigated the microheterogeneity of hybridoma products (HP) expressing the major idiotype (CRIA) associated with A/J antibodies to the p-azophenylarsonate (Ar) hapten group. The properties investigated were affinity for a phenylarsonate derivative and the fine specificity of the combining sites of the various HP. The fine specificity was approached by measuring relative affinities for a series of related haptens. It was found that, although variations exist, there are strong similarities in affinities and fine specificities of the antigen-binding sites of CRI+A HP. The range of affinities for (p-azobenzenearsonic acid)-N-3H-acetyl-L-tyrosine was 0.41 x 10(6)-2.2 x 10(6) M-1. In all cases the addition of a second ring structure (benzene or histidine) and an azo group greatly increased the binding affinity. Some differences in fine specificity among the HP were seen with respect to affinities for o-arsanilate or the arsanilate derivative of histidine. However, the two HP which are the strongest inhibitors in the conventional assay for CRIA were virtually identical to one another and to induced A/J anti-Ar antibodies in their fine specificities. Together with previous data on amino acid sequences and serological properties, the results indicate that, despite their microheterogeneity, members of the CRIA family are closely related in structure and hapten-binding specificity.

Animals↗
PubMed1982

Biologic activity of an idiotype-bearing suppressor T cell factor produced by a long-term T cell hybridoma.

Biologic activities and immunochemical characteristics of an azobenzenearsonate- (ABA)specific suppressor T cell factor produced by a longterm T cell hybridoma, F12, were studied. In vivo administration of F12 culture supernatant resulted in the suppression of ABA-specific delayed-type hypersensitivity (DTH) responses and the inhibition of priming for ABA-specific cytotoxic T lymphocyte responses. Moreover, F12 induced a second set of suppressor cells that act in the efferent phase of DTH. The active material in the F12 culture supernatant expressed major cross-reactive idiotypic (CRI) determinants of anti-ABA antibodies of A/J mice and I-J subregion-coded specificities but not express determinants of immunoglobulin constant regions. These results demonstrated that F12 is a functioning hybrid cell line of the first-order suppressor T cell subset.

Animals↗
PubMed1981

Monoclonal ant-idiotypic antibodies reactive with a highly conserved determinant on A/J serum anti-para-azophenylarsonate antibodies.

Previous reports have shown the A/J anti-para-azophenylarsonate (anti-Ar) antibodies that share a major cross-reactive idiotype (CRI) comprise a family of closely related but nonidentical molecules. Serological studies with CRI+ monoclonal anti-Ar antibodies have suggested the presence of a conserved idiotypic determinant within the family. The present study utilized monoclonal ant-idiotypic determinant within the family. The present study utilized monoclonal anti-idiotypic antibodies to define further the nature of the conserved idiotypic determinant. It was found that 8 of 10 CRI+ monoclonal antibodies possess an idiotypic determinant reactive with each of three monoclonal anti-idiotypic antibodies. In addition, approximately 60% of CRI+ serum anti-Ar antibodies reacted with one of the monoclonal anti-idiotypic preparations. The monoclonal anti-idiotypic antibodies react with an idiotope in the region of the hapten-binding site, as indicated by the ability of free haptens to inhibit idiotype-anti-idiotype interactions. Finally, two of three monoclonal anti-idiotypic antibodies suppressed the subsequent production of CRE+ serum anti-Ar antibodies when administered before antigen, without significantly affecting the total anti-Ar response.

Animals↗
PubMed1981

Antigen- and receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotype-positive, p-azobenzenearsonate-primed T cell target.

The suppressor pathway that regulates the T cell response to p-azobenzenearsonate (ABA)-coupled cells has been studied. It has been found that the ability of anti-idiotypic second-order T suppressor cells (Ts2) to inhibit T cell-dependent delayed-type hypersensitivity (DTH) responses depended upon the presence of cross-reactive-idiotype (CRI)-bearing T cells present in ABA-primed mice. This suppressor T cell subset, termed Ts2, so exists with CRI-negative T cells that mediate DTH in vivo. It appears that antigen-activated CRI+ Ts3 require signals from the anti-CRI Ts2 subset to suppress DTH reactions in an idiotype-nonspecific manner. The relevance of these observations to a comprehensive scheme of T and B cell regulation is discussed.

Animals↗
PubMed1981

Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells.

Azobenzenearsonate (ABA)-specific T cell-derived suppressor factor (TsF1) from A/J mice was used to induced second-order suppressor T cells (Ts2). Comparison of suppressor T cells induced by antigen (Ts1) with Ts2 induced by TsF1 revealed that Ts1 were afferent suppressors active only when given at the time of antigen priming, and not thereafter, whereas Ts2 could act when transferred at any time up to 1 d before antigen challenge for a delayed-type hypersensitivity response. This was true even when the recipient could be shown to be fully immune before transfer of Ts2, thus defining these cells as efferent suppressors. The anti-idiotypic specificity of the Ts2 was demonstrated by the ability of Ts to bind to idiotype (cross-reactive idiotype [CRI])-coated Petri dishes. A soluble extract from Ts2 (TsF2) was also capable of mediating efferent suppression that was functionally antigen- (ABA) specific. Comparison of TsF1 with this new factor, TsF2, revealed that both lack Ig-constant-region determinants, possess H-2-coded determinants, and show specific binding (to ABA and to CRI+-Ig, respectively). TsF1 acts in strains that differ with respect to H-2 and background genes, whereas TsF2 shows H-2- and non-H-2-linked genetic restrictions. This existence of H-2 restriction of TsF2 activity suggests that the apparent discrepancies in studies of H-2 restriction of TsF may be a result of the analysis of two separate classes of TsF, only one of which shows genetically restricted activity, thus unifying several models of suppressor cell activity.

Animals↗