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Biomedical subjects

E Mozes

Publications and source records attributed to E Mozes.

At least 163 records · Page 9Linked to original sources
PubMed1983

Fine specificity and idiotypic expression of monoclonal antibodies directed against poly(Tyr,Glu)-poly(DLAla)--poly(Lys) and its ordered analogue (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys).

In order to study the repertoire of poly(Tyr,Glu)-poly(DLAla)--poly(Lys) [(T,G)-A--L] specific antibodies, monoclonal antibodies were prepared by fusing myeloma cells with spleen cells from C3H.SW mice immunized with (T,G)-A--L and boosted with (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys)](T-T-G-G)-A--L]. Eleven clones which secreted homogeneous antibodies were obtained. In general, two families of monoclonal antibodies were detected: those which bind exclusively (T-T-G-G)-A--L and those which bind both (T-T-G-G)-A--L and (T,G)-A--L. Analysis for idiotypic expression revealed that only two antibodies (clones no. 103 and 160), which were found to be similar in their fine specificity, cross-reacted with antibodies against the major idiotypes of (T,G)A--L specific antibodies. Guinea-pig antibodies against clone no. 160 reacted with the polyclonal (T,G)-A--L specific antibodies, whereas antibodies against 103 monoclonal antibodies did not react with C3H.SW anti-(T,G)-A--L antibodies, but did cross-react with four other monoclonal antibodies. It appears that the idiotypic determinants expressed on polyclonal (T,G)-A--L specific antibodies are heterogeneous, and consist of at least two serologically different idiotypes detected by clones no. 103 and 160.

Animals↗
PubMed1982

Cellular analysis of specificity of antibodies and of delayed type hypersensitivity responses toward some structurally related synthetic antigens: boosting is determined by specificity of T cells.

The crossreactivity between the random synthetic polypeptide antigen poly(Tyr,Glu)-poly(DLAla)--poly(Lys) [(T,G)-A--L] and its ordered-sequence analogs (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys) [(T-T-G-G)-A--L] and (Tyr-Glu-Tyr-Glu)-poly(DLAla)--poly(Lys) [(T-G-T-G)-A--L] at the level of humoral and cellular responses was studied. For delayed type hypersensitivity responses, (T,G)-A--L-activated T cells could be challenged with the homologous antigen as well as with the ordered analogs. T cells activated by (T-T-G-G)-A--L could be challenged with either the homologous antigen or with (T,G)-A--L but not with (T-G-T-G)-A--L. Similarly, no cross stimulation was observed between (T-G-T-G)-A--L-activated cells and (T-T-G-G)-A--L, whereas (T,G)-A--L could challenge the latter cells to mediate significant responses. Similar but not identical cross reactions were observed when primed spleen cells or lymph nodes were transferred to irradiated recipients that were boosted for the production of antibodies. In contrast to observations at the level of cellular responses, (T-G-T-G)-A--L-primed spleen or lymph node cells could not be boosted with (T,G)-A--L for the production of detectable amounts of antibodies, although boosting with the homologous antigen resulted in significant levels of (T-G-T-G)-A--L-specific antibodies. Transfer experiments in which mixtures of T and B cells, each primed to a different ordered polypeptide antigen, were injected into irradiated recipients showed that successful cooperation occurs provided that the boost is given with the T-cell-specific antigen. The antibodies produced were specific to the antigen used for B-cell priming. The T-cell-B-cell collaboration probably occurs through specific determinants that are shared between the two antigens in which the ordered peptides are attached to the same multichain polymer and that are recognized by both the T and the B cells.

Amino Acid Sequence↗
PubMed1982

Genetic regulation of delayed-type hypersensitivity responses to poly (Tyr,Glu)-poly(DLAla)--poly(Lys): expression of the genetic defect in the induction and manifestation phases in H-2s and H-2f mice.

The genetic defect of H-2s and H-2s non-responder mouse strains in both the induction and manifestation phases of delayed-type hypersensitivity (DTH) responses to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys)[(T,G)-A--L] was analysed. Utilizing an in vitro system to activate DTH effector T cells, we observed that non-adherent T cells of (H-2f X H-2b) F1 or (H-2s X H-2b)F1 responder mice, could not be activated on antigen bearing adherent cells of H-2f or H-2s haplotypes. On the other hand, these T cells were effectively sensitized on adherent cells derived from either F1 or parental (H-2b) responder mice. These results indicate that in these mouse strains the genetic defect, in the induction phase of DTH, is expressed at the level of the antigen presenting cell. In subsequent experiments, we were able to "correct' the non-responsiveness of H-2s recipients by transfer of educated and irradiated (H-2s X H-2b)F1 T cells together with normal F1 adherent cells. Normal non-adherent and nylon wool enriched T cells failed to restore these responses. Similarly, antigen-pulsed F1 irradiated peritoneal exudate cells could stimulate DTH responses in SJL recipients of (SJL X C57BL/6)F1 (T,G)-A--L educated cells. The genetic defect of H-2s mice in the manifestation phase of the DTH reaction is thus also expressed on the antigen presenting cell.

Animals↗
PubMed1981

Enhancing effect of murine anti-idiotypic serum on the proliferative response specific for poly(LTyr, LGlu)-poly(DLAla)--poly(LLys)[(T,G)-A--L].

Murine anti-idiotypic serum against C3 H.SW anti-poly(LTyr, LGlu)-poly(DLAla)--poly(LLys)[(T,G)-A--L] antibodies was elicited in C57BL/6 mice. The effect of the anti-idiotypes on the proliferation of primed lymph node cells was investigated. The anti-idiotypic serum stimulated the proliferative response of the (T,G)-A--L-specific lymph node cells as well as of nylon wool-enriched T cells. In the presence of suboptimal doses of (T,G)-A--L, the addition of the anti-idiotypes enhanced the proliferation to the levels obtained with the optimal dose of (T,G)-A--L itself. These results suggest the existence of shared idiotypic determinants between antibodies and the (T,G)-A--L-specific proliferative T cells.

Animals↗
PubMed1981

Liposomes as immunological adjuvants in eliciting antibodies specific to the synthetic polypeptide poly(LTyr, LGlu)-poly(DLAla)--(LLys) with high frequency of site-associated idiotypic determinants.

The antibody response to the synthetic polypeptide, poly(LTyr, LGlu)-poly(DLAla)--poly(LLys), [(T,G)-A--L], injected entrapped in liposomes which served as adjuvant has been analyzed. The liposomes used were composed of phosphatidylcholine, cholesterol, dicetylphosphate and DL alpha-tocopherol (molar ratios as 4:3:0.1:0.5) and therefore, were negatively charged. Since the (T,G)-A--L is also negatively charged, no free complexes were formed. The (T,G)-A--L was found to be entrapped inside the enclosed volume of the liposomes, and no (T,G)-A--L antigenic determinants could be detected on the liposomal membranes. Injection of high-responder C3H.SW (H-2b) mice with (T,G)-A--L-bearing liposomes demonstrated that the i.p. and the i.v. routes of immunization were efficient in eliciting (T, G)-A--L specific antibodies, whereas the i.d. injection led to poor antibody responses. The latter route of immunization is the most effective when (T,G)-A--L is injected in complete Freund's adjuvant (CFA). When low doses (0.1 and 1 microgram) of (T, G)-A--L were used for immunization, the liposomes were better adjuvants than CFA. The effectiveness of the liposomes as immunological adjuvants was also shown in their ability to induce high-potential, primed memory cells. The pattern of low (H-2k,a) and high (H-2b) responsiveness to (T,G)-A--L was retained following immunization with (T,G)-A--L entrapped in liposomes, as tested in two pairs of congenic strains. (T,G)-A--L-specific antibodies induced by injection with 1 microgram antigen entrapped in liposomes bear the (T,G)-A--L site-related idiotypic markers of C3H.SW (Igh-1a) mice in a significantly higher frequency than the homologous idiotypes, namely the antibodies elicited in this strain against (T,G)-A--L in CFA. Thus, liposomes may serve as adjuvants for the production of relatively restricted (T,G)-A--L-specific antibodies of high quality.

Adjuvants, Immunologic↗
PubMed1981

Immune response potential to poly(Tyr,Glu)-poly(DLAla)--poly(Lys) of human T cells of different donors.

Human peripheral blood T cells of normal donors were activated in vitro with autologous adherent cells pulsed with poly(LTyr,LGlu)-poly(DLAla)--poly(LLys) [abbreviated (T,G)-A--L]. The "educated" T cells were tested: (i) for their ability to produce a (T,G)-A--L-specific T cell-replacing factor in the cooperation with B cells for antibody responses in vivo or in vitro and (ii) for their ability to proliferate in the presence of a second stimulus of (T,G)-A--L. Results of screening of 66 donors demonstrated that educated T cells of about 50% of the donors produced an active (T,G)-A--L-specific factor, whereas activated cells of only half of the factor producers were capable of proliferating in the presence of the antigen. Thus, as reported for all other species studied, human individuals differ in their response potential to (T,G)-A--L.

Antibody Formation↗
PubMed1980

Elicitation of delayed-type hypersensitivity responses to poly(L-Tyr,LGlu)-poly(DLAla)--poly(LLys) by anti-idiotypic antibodies.

The in vivo effect of murine anti-idiotypic serum against C3H.SW anti-poly(LTyr,LGlu)-poly(DLAla)-(LLys) [(T,G)-A--L] antibodies on delayed type hypersensitivity responses to (T,G)-A--L was studied. Anti-idiotypic serum could challenge DTH responses in C3H.SW mice transferred with antigen-sensitized T cells. The elicitation activity was shown to be antigen and strain specific. With H-2-compatible (but allotype different) strain combinations of (T,G)-A--L-educated T cells and recipients, we were able to show that the biological effect of the anti-idiotypic serum is expressed on the first antigen-sensitized idiotype-positive radioresistant T cell, but not on the proliferating normal cells of recipient origin that participate in the efferent phase of delayed-type hypersensitivity responses to (T,G)-A--L.

Animals↗
PubMed1980

T-cell hybridoma bearing heavy chain variable region determinants producing (T,G)-A--L-specific helper factor.

Thymus-derived lymphocytes (T cells) exert their regulatory effect (help or suppression) on the antibody production by B cells either by direct cell to cell interaction or by soluble mediators or factors. The low frequency of specific T cells, the heterogeneity of their responses and their relatively short life span have hampered the molecular characterization of the antigen recognition unit of T cells, and its structure is largely unknown. The lymphocyte hybridization technique, which has been found very useful for the production of B-cell hybridomas secreting specific monoclonal antibodies, has also been used for the generation of homogeneous and stable T-cell hybridomas with unlimited growth potential. So far the only specific effector function demonstrated in the established T hybridomas is the property to generate a factor(s) which suppresses antibody responses. We now describe the establishment of hybrid lines which exhibit characteristic T-cell markers. One of the hybridomas (denoted R-9) releases into the culture supernatant factor(s) with helper activity specific to the synthetic polypeptide (T,G)-A--L and bears surface determinants of the immunoglobulin heavy chain variable region (VH). Such hybrid cell lines are of great value for studies on the nature of the T-cell receptor.

Animals↗
PubMed1980

Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys). II. Evidence for a T-T-cell collaboration in delayed-type hypersensitivity responses and for a T-cell defect at the efferent phase in nonresponder H-2k mice.

The intercellular interactions and the site of the genetic defect in delayed-type hypersensitivity (DTH) response to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys) [(T,G)-A--L] has been studied in a system where the T-cell education phase was separated from the efferent phase. In the cellular response, T-T-cell collaboration is required, because T cell-depleted mice were unable to manifest DTH responses after they were transferred with educated and irradiated T cells. Reconstitution of adult thymectomized mice that were irradiated and supplemented with bone marrow cells after treatment with anti-Thy-1.2 serum and complement, with T cells but not with accessory cells gave rise to significant responses. Educated, radioresistant cells required the presence of normal radiosensitive T cells for successful DTH responses to (T,G)-A--L. The genetic defect of nonresponder H-2k and H-2a mice has been located in the above-mentioned, second T-cell population that participates in the efferent phase of this immune reaction. Further characterization revealed that the educated cells are of the Lyt1+ phenotype and that the second normal T cells are expressing the Lyt 1+,2+,3+ phenotype. Thus, the genetic defect of H-2k and H-2a mice in the DTH response to (T,G)-A--L is expressed on the non-antigen-stimulated Lyt 1+,2+,3+ T cells.

Animals↗
PubMed1980

Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGu)-poly(DLAla)--poly(LLys). I. Expression of the genetic defect at two phases of the immune process.

Delayed-type hypersensitivity (DTH) responses served in this study as an experimental model for the analysis of genetic regulations of T-cell responses. Educated irradiated cells from H-2b mice mediated responses in syngeneic recipients, whereas mice of the a, d, f, k, and s haplotypes were nonresponders to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys)[(T,G)-A--L]. These results suggest that cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was shown for humoral responses. Educated irradiated T cells of F1 hybrids between high and low responders mediated DTH responses, which indicates that the gene(s) controlling the DTH responses is dominant. To analyze the genetic defect in DTH responses to (T,G)-A--L, we separated the T-cell activation phase from the effector phase that was determined in recipient mice. Two types of nonresponders were observed: (a) When lymphocytes of the a or k haplotypes were educated in a syngeneic environment and then transferred into hybrids between the parental (nonresponder x responder) F1 recipients, DTH responses could have been manifested. (b) On the other hand, no DTH responses could be mediated by transferring educated cells of the H-2s or H-2f origin into the appropriate F1 recipients. In addition, irradiated F1 cells that had been activated to (T,G)-A--L could not mediate DTH responses in both types of nonresponder recipients. These results suggest that T cells of H-2k or H-2a mice can be activated to generate DTH responses to (T,G)-A--L and that the defect in these mouse strains is expressed in another cell population needed for the manifestation of the DTH reaction in the recipient mice. In contrast, T cells of H-2s and H-2f origin cannot be activated to (T,G)-A--L and, thus, fail to manifest DTH responses.

Animals↗
PubMed1980

Efficient genetically controlled formation of antibody to a synthetic antigen [poly(LTyr, LGlu)-poly(DLAla)- -poly(LLys)] covalently bound to a synthetic adjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine).

The synthetic polypeptide antigen poly(LTyr, LGlu)-poly(DLAl)- -poly(LLys)[T,G)-A- -L] was covalently linked to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal adjuvant-active structure that can substitute for Mycobacteria in complete Freund's adjuvant. When injected in aqueous solution into mice, the completely synthetic conjugate elicited significant antibody responses specific to (T,G)-A- -L, whereas (T,G,)-A- -L alone administered under the same conditions did not lead to antibody production. The conjugate was much more efficient in eliciting (T,G)-A- -L responses than was a mixture of DMP and (T,G)-A- -L. One hundred micrograms of MDP mixed with 10 micrograms of (T,G)-A- -L resulted in production of (T,g)-A- -L-specific antibodies. However, the titers obtained were much lower than those observed with 10 micrograms of the conjugate, MDP-(T,G)-A- -L, which contained less than 1 microgram of MDP. MDP was enhanced when the mixture was administered in incomplete Freund's adjuvant, the adjuvant did not significantly affect the (T,G)-A- -L-specific antibody responses in mice immunized with MDP-(T,G)-A- -L. The isoelectric focusing pattern of antibodies obtained with MDP-(T,G)-A- -L was similar to that obtained after immunization with (T,G)-A- -L in complete Freund's adjuvant. The pattern of high-responder and low-responder mice to (T,G)-A- -L, the immune response to which is genetically controlled, was retained when MDP-(T,G)-A- -L was used as the immunogen. Conjugation of (T,G)-A- -L was creased the immunogenicity of MDP and affected its biological properties. It is thus possible to obtain efficient immune responses to synthetic polypeptide antigens that produce poor reactions when injected in aqueous solution by conjugating them to small molecular weight synthetic adjuvants.

Acetylmuramyl-Alanyl-Isoglutamine↗