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E Benjamini

Publications and source records attributed to E Benjamini.

At least 37 records · Page 2Linked to original sources
PubMed1987

Resistance of California ground squirrels (Spermophilus beecheyi) to the venom of the northern Pacific rattlesnake (Crotalus viridis oreganus): a study of adaptive variation.

Recent studies have documented natural resistance to snake venom in a number of diverse mammalian species. The present paper documents for the first time variation in such resistance within one single species, the California ground squirrel (Spermophilus beecheyi). This species is a frequent prey of the northern Pacific rattlesnake (Crotalus viridis oreganus) in certain habitats. Venom resistance was tested directly in two populations of ground squirrels by injection of 1-40 mg/kg venom doses. One population was obtained from a habitat with a high rattlesnake density; the other population came from a rattlesnake-free habitat. Dramatic differences in the response to venom between these populations were manifested, based on a variety of criteria, such as mortality, necrosis and healing time. Resistance to venom was also examined by LD50 tests in groups of mice pre-injected with ground squirrel sera from three rattlesnake-adapted California populations and a non-adapted Arctic population (S. parryii) from snake-free central Alaska. The California ground squirrel sera were 3.3-5.3 times more effective in the in vivo neutralization of venom than the sera from Arctic ground squirrels. Moreover, the level of protection by the sera as reflected by the LD50 values was highly correlated (P less than 0.005) with the level of in vitro squirrel serum-venom binding as quantified by radioimmunoassay (RIA). A subsequent RIA revealed that binding levels of sera from 14 California ground squirrel populations correlated significantly (P less than 0.025) with local rattlesnakes densities; i.e. sera pools from populations sympatric with rattlesnakes exhibited the highest binding, whereas populations living in habitats where rattlesnakes are rare or absent typically exhibited the lowest binding levels, several of which approximated the Arctic control. Taken together, these results demonstrate intraspecific variation that is probably the result of differential natural selection due to northern Pacific rattlesnakes. This intraspecific variation should be taken into consideration when testing for natural resistance in wild-caught species.

Adaptation, Physiological↗
PubMed1986

Antigenic requirements for T-cell activation: reconstitution of a functional antigen from an inactive peptide portion of an antigen conjugated to protein carriers.

The structural features of an antigenic peptide required for T-cell activation were examined by a novel approach: an active antigen was constructed from an inactive peptide portion of the original antigen by conjugating it to various proteins. An eicosapeptide, peptide 8, representing residues 103-112 of the tobacco mosaic virus protein (TMVP), was utilized as the model antigen for these studies. While peptide 8 was able to stimulate, in vitro, T-cells from peptide 8 primed mice, synthetic peptides representing various portions of peptide 8 were unable to activate these cells. Although the amino-terminal undecapeptide of peptide 8 (residues 93-103 of TMVP) was unable to activate T-cells from peptide 8 primed mice, conjugates which consisted of this undecapeptide coupled to certain proteins were capable of inducing antigen-specific proliferation of these T-cells. These results identify two structural antigenic features essential for T-cell activation: a T-cell-recognizable epitope within the amino-terminal undecapeptide of peptide 8 and a second region provided by the carboxy-terminal half of peptide 8 or by protein carriers. Potential roles for this second region include providing a site for antigen interaction with Ia molecules on the antigen-presenting cell or, alternatively, providing amino acids important in stabilizing the binding of the T-cell antigen receptor. The results suggest that the recognition of this second region exhibits only a limited specificity.

Animals↗
PubMed1986

Cell activation and immunogenicity.

There is presently great interest in the production of synthetic vaccines which utilize as immunogens peptides representing portions of protein antigens, either free or conjugated to protein carriers. The use of such immunogens raises questions regarding the cells which are activated an the characteristics of the resulting immune response. Using the tobacco mosaic virus protein (TMVP) as a model antigen, immune induction by the protein and by synthetic vaccines related to this protein was investigated. Specifically we have compared immune induction by the parent protein, an unconjugated eicosapeptide representing residues 93-112 of the protein, and an immunogen consisting of the C-terminal decapeptide of the above eicosapeptide conjugated to the protein carrier KLH. The comparison led to the following conclusions: Immunization with the free eicosapeptide but not with its C-terminal decapeptide leads to the activation of T and B lymphocytes. Immunization with the free eicosapeptide or with its C-terminal decapeptide-KLH conjugate induces antibodies capable of reacting with the parent protein. The isotype composition of the antibodies induced by these immunogens is similar to that induced by immunization with the whole protein. The fine specificity of the antibodies induced by all three immunogens is similar. However, the antibody populations induced by the synthetic immunogens may be devoid of one or more clonotypes depending upon constraints imposed by cellular interaction. Antigen specific T helper cells do not seem to influence the fine specificity of antibodies induced to a given epitope. Comparison of the induction of memory responses by the three immunogens led to the conclusion that immunization with the peptide hapten conjugated to the heterologous carrier KLH does not lead to an anamnestic antibody response upon encounter with the native protein. Immunization with an immunogenic peptide representing a portion of the protein recognized by T and B lymphocytes leads to an anamnestic antibody response upon encounter with the native protein.

Animals↗
PubMed1985

Immune induction by a protein antigen and by a peptide segment of the protein.

The immune induction by a protein (the tobacco mosaic virus protein-TMVP) was compared to the immune induction by the free, non-conjugated eicosa tryptic peptide fragment of the protein (tryptic peptide 8 representing residues 93-112 of the protein). The results demonstrated that like TMVP, peptide 8 was immunogenic in A/J mice. TMVP and peptide 8 do not cross react on the T cell level. However, immunization with TMVP or with peptide 8 induces antibodies which react with both TMVP and peptide 8. Characterization of the antibodies produced by both immunogens revealed that: their isotope composition is similar with IgG1 and IgG2 being the predominant isotypes; this composition indicates that both immunogens are T cell dependent antigens, the antibodies induced by TMVP and by peptide 8 are directed against the C-terminal decapeptide portion of peptide 8 (residues 103-112 of the protein), the fine specificity of these antibodies is the same. These results, and results of adoptive transfer experiments, indicate that antigen specific T cells had no effect on the expression of the fine antibody specificity. The results demonstrate the feasibility of immunizing with a portion of a protein for the purpose of inducing antibodies with the same isotype composition and specificity towards a protein epitope as those induced by immunization with the whole protein.

Amino Acid Sequence↗
PubMed1985

The idiotypic characterization of the immune response to a defined epitope of a protein antigen and the specific in vivo suppression of the immune response to this epitope by anti-idiotypic antibodies.

C10, a monoclonal antibody of C3H.SW (CSW) origin, binds a decapeptide epitope of the tobacco mosaic virus protein (TMVP) representing residues 103-112 of the protein. In vivo administration of syngeneic anti-idiotypic antibodies to C10 (anti-C10) prior to immunization with TMVP suppressed the expression of antibodies to this decapeptide determinant in CSW mice without a significant reduction of the total anti-TMVP titer. The suppression could not be overcome with repeated challenges by antigen even 6 months after administration of anti-C10. Analysis of anti-C10 showed that it contains antibodies to at least two idiotopes found on C10. One of these idiotopes, C10-Idm, is found on a very small fraction of CSW anti-TMVP antibodies capable of binding the decapeptide epitope. The other idiotope, C10-IdX, is found on most of the anti-TMVP antibodies which bind the decapeptide determinant. With synthetic analogues of the decapeptide determinant, a correlation was established between the presence of the C10-IdX and the fine specificity of the decapeptide-binding antibodies. The studies reported herein demonstrate that anti-idiotypic antibodies are potent modulators of the immune response and that the C10-IdX is important in the determination of the fine specificity of antibodies to this decapeptide epitope of TMVP.

Animals↗
PubMed1984

The antibody response to a single antigenic determinant of the tobacco mosaic virus protein: analysis using monoclonal antibodies, mutant proteins and synthetic peptides.

Three hybridomas were selected which secreted monoclonal antibodies specific to a decapeptide determinant representing residues 103-112 of the tobacco mosaic virus protein ( TMVP ). A series of proteins from several strains of TMV which differ in the amino acid sequence in this region of the protein were used as probes for specificity analysis. The fine-specificity analysis was extended by assessing the binding of the antibodies with a panel of synthetic peptide analogues of the native decapeptide with amino acid substitutions at different locations. The binding of each synthetic peptide with each of the monoclonal antibodies was determined by the ability of the radiolabeled peptide to bind with the antibody. The binding of the decapeptide with antibodies was determined by equilibrium dialysis; the relative binding affinity of each peptide of the panel was determined by the capacity of the peptide to inhibit the binding between the antibody and the radiolabeled native decapeptide. The results demonstrated that a panel of synthetic peptide analogues constitutes a powerful tool for discerning the fine specificity of antibodies directed to a given determinant of a protein antigen. The data indicated that, although all of the antibodies recognized the same nominal decapeptide determinant, their binding with the different mutant proteins or with the synthetic peptides of the panel differed greatly, indicating dramatic differences in their fine specificity. The existence of such differences should be taken into consideration when assessing residues of a protein antigen that are involved in antibody binding. The differences which were found in monoclonal antibodies produced following immunization with the whole TMVP reflect differences which occur in heterogeneous serum antibody populations and point out the complexity of antigenic recognition even of as small an epitope as a decapeptide.

Amino Acid Sequence↗
PubMed1983

Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis.

Previously, it was shown that arthroconidia of Coccidioides immitis appear to inhibit phagosome-lysosome fusion and survive within normal mouse peritoneal macrophages. However, when these macrophages are exposed to antigen-stimulated T lymphocytes from immune mice, activation occurs, leading to enhanced phagosome-lysosome fusion and killing of C. immitis. Results indicate that the activation of macrophages can be effected after incubation with soluble lymphocyte product(s) (lymphokines). The activation of macrophages results if the macrophages are exposed to the lymphokine before, but not after, infection. The results indicate that the lymphocyte population responsible for the elaboration of the lymphokine is phenotypically Lyt1+2- and that activation of macrophages by the lymphokine can occur across H-2 histocompatibility barriers.

Animals↗
PubMed1983

Functional heterogeneity of memory B lymphocytes: in vivo analysis of TD-primed B cells responsive to secondary stimulation with TD and TI antigens.

The functional heterogeneity of memory B cells induced by a single determinant, consisting of a decapeptide representing amino acid residues 103-112 of tobacco mosaic virus protein (TMVP), was analyzed. Decapeptide specific antibodies were elicited in mice adoptively transferred with TMVP-immune spleen cells when challenged with TMVP, decapeptide conjugated to succinylated human gamma-globulin (SHGG), or decapeptide conjugated to Brucella abortus (BA). Whereas secondary stimulation by either TMVP or decapeptide-SHGG was dependent on appropriately primed T cells, stimulation by decapeptide-BA was independent of conventional T cell help. Furthermore, memory B cells responsive to TMVP (TD), decapeptide-SHGG (TD), or decapeptide-BA (TI. 1 prototype) were shown to consist of overlapping populations because adoptive recipients of TMVP-primed cells challenged simultaneously with TD and TI decapeptide antigens did not result in a higher antibody response than that elicited by one of the TD antigens injected alone. However, decapeptide-BA consistently induced a smaller antidecapeptide response than either TMVP or decapeptide-SHGG. This suggested that only a fraction of the memory B cell population which was activated by the original priming antigen (thymus-dependent) was also responsive to secondary in vivo stimulation by the priming hapten conjugated to Brucella abortus. Detailed analyses of the antibodies induced in the recipients of TMVP-immune spleen cells after secondary challenge with either TMVP, decapeptide-SHGG, or decapeptide-BA failed to distinguish between the responsive memory B cells; the antidecapeptide antibodies induced by all three immunogens shared the same fine specificities and immunoglobulin isotype composition. These data are viewed as further evidence that subsets of TD-primed B cells, which may display differential sensitivity to cross-stimulation with TD and TI forms of the antigen, represent distinct stages of memory B cell maturation within a common B cell lineage. In support of this conclusion, we establish a developmental relationship between TI and/or TD responsive decapeptide memory B cell in the following communication.

Animals↗
PubMed1983

Two stages of b cell memory development expressing differential sensitivity to stimulation with thymus-dependent and thymus-independent antigenic forms.

We have shown that spleen cells specifically primed to the decapeptide determinant (a.a. 103-112) of the thymus-dependent (TD) antigen, tobacco mosaic virus protein (TMVP), can be secondarily stimulated to antibody synthesis by either TD or TI forms of the decapeptide. Further, TD- and TI-responsive memory B cells consisted of overlapping populations which were indistinguishable by the specificity and isotype composition of the antibodies which they synthesized. In the present study, two functionally distinct but developmentally related memory B cell subsets were identified by their differential sensitivity to repeated in vivo stimulation with various combinations of TD and TI decapeptide antigens. One subset of memory B cells responded only to TMVP or decapeptide conjugated to succinylated human gamma-globulin (SHGG) with a strict requirement for carrier-primed theta-positive cells. Secondary challenge with these two TD antigens elicited antidecapeptide antibodies and specific memory regeneration. This TD-responsive memory B cell subset contained the precursors of a second memory B cell subset which was activated by decapeptide-Brucella abortus (TI.1 prototype), as well as by TMVP or decapeptide-SHGG. Stimulation of the second memory B cell subpopulation by decapeptide-BA (previously shown not to be dependent on conventional T cell help) was typified by differentiation into antibody-forming cells without significant memory regeneration.

Animals↗
PubMed1983

The antibody response to a single antigenic determinant of the tobacco mosaic virus protein (TMVP): effects of allotype-linked genes and restricted heterogeneity of the response.

The antibody response to a decapeptide antigenic determinant representing residues 103 to 112 of the tobacco mosaic virus protein (TMVP) was studied with the synthetic decapeptide and a panel of its synthetic analogues. The anti-decapeptide response was found to be of restricted heterogeneity and was regulated by heavy chain allotype-linked (V region) genes on at least two levels. One level was whether or not a significant antibody response was made to the decapeptide determinant. Thus, strains with the Igh haplotypes j, o, e, and n were high responders, whereas strains with haplotype Ighb were low responders. The second level of V region gene control was with regard to the fine specificity of the anti-decapeptide antibodies produced. Using the peptide panel to analyze fine specificity, we define two new V region genetic markers, VH-TMVPj and VH-TMVPe.

Animals↗
PubMed1982

Induction of tolerance to a soluble antigen following irradiation and bone marrow reconstitution.

Antigen-specific tolerance was induced in mice by lethal irradiation followed by reconstitution with syngeneic, anti-T-cell-treated bone marrow and injection of the protein antigen lysozyme. Animals tolerized with lysozyme responded normally to a second antigen, sheep red blood cells, and animals treated with the same tolerizing regimen using a different protein antigen, bovine serum albumin, responded normally to lysozyme. Challenge of the tolerant mice with lysozyme covalently coupled to LPS induced an antilysozyme response indicating that if tolerance was expressed on the B-cell level that antigen-specific B-cells were still present. These results eliminate clonal abortion and clonal selection as the mechanism of tolerance generation. The tolerance generated by this procedure is either expressed on the T-cell level or is produced by a state of B-cell clonal anergy which can be overcome by the use of antigen coupled to lipopolysaccharide.

Animals↗
PubMed1981

Effects of prostaglandin synthesis inhibition on the immune response.

Inhibition of prostaglandin synthesis at the time of antigen presentation was used to test the role of prostaglandins in the inductive stage of the in vivo immune response to several antigens. Indomethacin and Ro 20-5720, two prostaglandin synthesis inhibitors, produced a several-fold enhancement of the primary immunoglobulin (Ig) M and IgG anti-sheep red blood cell plaque-forming cell (PFC) response in CAF1 mice. Indomethacin and Ro 20-5720 also enhanced the antibody response to chicken serum albumin (CSA) in buffered saline. However, the antibody response to CSA in Freund's adjuvant was reduced by indomethacin treatment. Indomethacin treatment enhanced the PFC response to a chicken lysozyme-lipopolysaccharide conjugate, and did not greatly affect the PFC response to pneumococcal polysaccharide. The allogeneic cytotoxic response to the El-4 tumor line was delayed by indomethacin treatment and, since this tumor does not synthesize prostaglandins, we speculate that prostaglandin synthesis by the host is important in the generation of a cytotoxic response to this tumor. It is concluded that the role of prostaglandins in the induction of the immune response varies, and can be proinductive or anti-inductive, depending on the eliciting antigen.

Animals↗
PubMed1981

Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro.

Peritoneal macrophages from normal mice phagocytized arthroconidia and endospores of Coccidioides immitis without affecting the viability of the spores within 4 h after infection. In contrast, macrophages, when infected in the presence of lymphocytes from immune mice, significantly reduced the viability of phagocytized endospores and arthroconidia. The inability of macrophages from normal mice to kill C. immitis may in part be explained by the observation that C. immitis appeared to inhibit fusion of the phagosomes containing fungal spores with the lysosomes within the macrophages. However, fusion of phagosomes containing spores and lysosomes was observed in macrophages infected in the presence of lymphocytes from immune mice.

Animals↗
PubMed1980

Differential activation of primary and memory "B" lymphocytes.

Immunization of certain strains of mice with the tobacco mosaic virus protein (TMVP) elicits antibodies capable of binding with a decapeptide representing residues 103-112 of TMVP. However, immunization of mice with decapeptide conjugated to a variety of carriers failed to elicit antibodies to the decapeptide in spite of the fact that antibodies were induced to the carriers or to nonrelated peptides similarily conjugated to the carriers. In contrast to the conjugates inability to induce a primary anti-decapeptide response, the conjugates were able to elicit a secondary anti-decapeptide response. Thus, when irradiated mice were transplanted with syngeneic TMVP-primed B cells and carrier-primed T cells, secondary challenge with the decapeptide on the carrier elicited an excellent secondary anti-decapeptide response. Furthermore, the titer and specificity of the antibodies so induced were the same as that induced by secondary challenge with TMVP. These results suggest a difference between primary and memory B cells in their requirements for activation.

Animals↗
PubMed1980

Chemoimmunotherapy for canine lymphosarcoma: a prospective evaluation of specific and nonspecific immunomodulation.

Fifty-six dogs were given chemoimmunotherapy for spontaneous lymphosarcoma. The dogs had been given identical combination chemotherapy (8 weeks) for induction of remission, and after achieving complete clinical remission, they were randomly assigned to one of three treatment groups to evaluate immunotherapy as a method ancillary to chemotherapy to maintain or extend the remission. For immunostimulation, one-third of the dogs were given chemically modified autochthonous tumor cell extract in Freund's complete adjuvant (FCA), one-third were given nonmodified tumor cell extract in FCA, and one-third were given FCA alone. A historical control population of dogs given the same chemotherapy was used for comparison. Of the 56 dogs, 50 (89.3%) achieved initial remission, but 18 of the latter relapsed clinically during the initial 8-week-chemotherapy regimen. The remaining 32 dogs (or 57.1% of the original 56 dogs) were subsequently given immunotherapy. Duration of remission and survival time were recorded. The median remission duration and survival time for all dogs given immunotherapy following cytoreductive chemotherapy were significantly longer than the historical control population given chemotherapy alone. However, there was no significant difference in remission duration or survival among the three immunotherapy groups.

Animals↗
PubMed1980

The immunoregulatory role of antigen-antibody complexes. I. Assessment of B and T-cell responses.

The capacity of ovalbumin-anti-ovalbumin complexes to prime T cells preferentially without concomitant induction of antibody synthesis was investigated. Whereas free antigen injection into mice primed T and B lymphocytes and induced antibody production, injection of antigen-antibody complexes did not result in antibody production but did result in T-cell priming. However, the data suggest that, notwithstanding the lack of induction of antibody synthesis by immune complexes, a low degree of B-cell priming by the complex occurred; this priming was of IgM precursors only. The results indicate that the immunoglobulin isotype composition of the complex may be important to this preferential effect.

Animals↗