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Biomedical subjects

E Mozes

Publications and source records attributed to E Mozes.

At least 181 records · Page 10Linked to original sources
PubMed1980

Specificity of genes controlling immune responsiveness to (T,G)-A--L and (Phe,G)-A--L.

Mice possessing the H-2b haplotype are high responders to the cross-reactive antigens (T,G)-A--L and (Phe,G)-A--L whereas mice with the H-2k haplotype respond only to (Phe,G)-A--L. On the level of cross-immunization we have demonstrated that either (Phe,G)-A--L or (T,G)-A--L primed high responder C3H.SW (H-2b) mice could be boosted with both antigens. On the other hand, low responder C3H/DiSn (H-2k) mice which were primed to (Phe,G)-A--L and thus possess (T,G)-A--L specific antibodies, could not be boosted with (T,G)-A--L to mount a secondary response. Only (Phe,G)-A--L primed and boosted H-2k mice produced high levels of (T,G)-A--L reactive antibodies. Furthermore, the binding of the anti-(Phe,G)-A--L antibodies of either C3H/DiSn or C3H.SW mice to 125I-(T,G)-A--L was better inhibited by guinea-pig anti-idiotypes than the binding of C3H.SW anti-(T,G)-A--L antibodies which are the homologous idiotypes (T,G)-A--L was found to be an equally efficient tolerogen in both high and low responder mice. Thus, when C3H.SW and C3H/DiSn mice were injected with a tolerogenic dose of (T,G)-A--L and then immunized with (Phe,G)-A--L, they were found to be tolerant to (T,G)-A--L antigenic determinants, since they produced only the unique antibodies to (Phe,G)-A--L. These results suggest that the H-2 linked Ir genes controlling antibody response to (T,G)-A--L are not involved in the induction of tolerance to (T,G)-A--L.

Animals↗
PubMed1979

Change in specificity of antibodies to a random synthetic branched polypeptide in mice tolerant to its ordered analogs.

The crossreactivity between the random synthetic polypeptide antigen, (Tyr,Glu)-poly(DLAla)- -poly(Lys), and its ordered sequence analogs, (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) and (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys), has been studied on the level of tolerance induction. Induction of tolerance to the random (Tyr,Glu)-poly(DLAla)- -poly(Lys) affected the response of the tolerant mice to the homologous antigen as well as to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys), which was shown previously to represent the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys). In contrast, these mice responded with high antibody titers to the hardly crossreacting (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Mice tolerant to the ordered peptide antigen (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys) did not respond to the homologous polypeptide; however, their immune response to either (Tyr-Glu)-poly(DLAla)- -poly(Lys) or (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) was not affected. Mice that were tolerant to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) responded well to (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Furthermore, these mice produced high antibody titers after immunization with the random (Tyr,Glu)-poly(DLAla)- -poly(Lys). However, the antibodies produced were not specific to the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys), namely, Tyr-Tyr-Glu-Glu, but were directed to minor determinants of the random polypeptide, including Tyr-Glu-Tyr-Glu, which are not immunopotent when nontolerant mice are immunized with (Tyr,Glu)-poly(DLAla)- -poly(Lys). Thus, whereas antigenic specificity reflects itself also at the level of tolerance induction, the animals that had been made tolerant are capable of responding to previously silent antigenic determinants.

Animals↗
PubMed1978

The nature and functions of specific immune response genes and their products.

Antibodies produced by inbred mouse strains immunized with the random synthetic polypeptide poly (Tyr,Glu)-poly(DLAla)--polyLys denoted (T,G)-A--L were found to be specific mainly to the ordered peptide Tyr-Tyr-Glu-Glu. Low responder H-2k mice, upon immunization with either the random (T,G)-A--L or the ordered (T-T-G-G)-A--L coupled to methylated bovine serum albumin (MBSA), produce antibodies with comparable titers to those observed in high responder H-2b mice following immunization with the antigens alone or with their complexes with MBSA. A comparison of the above antibodies have led to the conclusion that low responder mice, upon immunization with the synthetic antigens complexed with MBSA, produce antibodies of the same specificity and quality as those of high responders (as shown by the isoelectric focusing technique) and they also have the same affinity and heterogeneity as antibodies of H-2b mice (measured by equilibrium dialysis and antigen binding capacity assay). Anti-idiotypic sera to anti-T,G)-A--L antibodies of C3H.SW (H-2b,Ig-1a) mice were raised in guinea pigs. C3H.SW anti-(T,G)-A--L antibodies from different pools cross reacted idiotypically. Anti-(T,G)-A--L antibodies of CWB (H-2b, Ig-1b) mice did not react with the anti-idiotypic serum suggesting linkage between the genes coding for idiotypes and allotypes. C3H/DiSn (H-2k, Ig-1a) anti-(T,G)-A--L antibodies elicited by immunization with (T,G)-A--L complexed to MBSA reacted with the anti-idiotypic serum to the same degree as C3H.SW anti-(T,G)-A--L antibodies, confirming the similarity between the high and low responder anti-(T,G)-A--L antibodies. C3H.SW (H-2b) mice as well as C3H/DiSn (H-2k) mice were found to be capable of producing an antigen specific factor from "educated" T cells which replaces the helper effect of T cells in the process of antibody production. On the other hand B cells of H-2k mice were not triggered by a factor of either high or low responder specific T cells. The activity of a C3H.SW (T,G)-A--L specific T cell factor was removed after passage on a Sepharose column coupled to the anti-idiotypic serum prepared against C3H.SW anti-(T,G)-A--L antibodies, suggesting similarity between the antigen specific T cell factor and the B cell recognition system. A (T,G)-A--L specific factor produced by C3H/DiSn (H-2k, Ig-1a) "educated" T cells reacted with the anti-idiotypic serum as well. Thus, C3H.SW high and C3H/DiSn low responder (T,G)-A--L specific T cell factors cross react at the level of their binding site for antigen.

Alanine↗
PubMed1978

Specificity and crossreactivity of idiotypes of murine antibodies induced by poly(Tyr,Glu)-poly(DLAla)-poly(Lys) and poly(Phe,Glu)-poly(DLAla)-poly(Lys).

Antibodies elicited against the two synthetic polypeptides, poly(Tyr,Glu)-poly(DLAla)-poly(Lys) [(T,G)-A-L] and poly(Phe,Glu)-poly(DLAla)-poly(Lys) [(Phe,G)-A-L], are crossreactive although the humoral responses to these immunogens are under different genetic controls. The fine specificity of the antibodies elicited by the two polypeptides was studied in the present work. Antisera against (Phe,G)-A-L bind both (125)I-labeled (T,G)-A-L and iodinated modified (Phe,G)-A-L. However, while the binding to (T,G)-A-L could be inhibited completely with the two antigens, the binding to (Phe,G)-A-L was inhibited completely with (Phe,G)-A-L and only partially with (T,G)-A-L. The binding of (125)I-labeled (T,G)-A-L to antisera against (T,G)-A-L was inhibted more efficiently by the homologous antigen than by (Phe,G)-A-L although both antigens completely inhibited the binding. (T,G)-A-L specific antibodies were purified on (T,G)-A-L immunoadsorbents from antisera of high and low responder mice to (T,G)-A-L immunized with (Phe,G)-A-L. (Phe,G)-A-L specific antibodies that did not bind (T,G)-A-L were isolated from the effluent of these columns. By use of anti-idiotypic antibodies of guinea pig against C3H.SW antibodies to (T,G)-A-L it was shown that (T,G)-A-L specific antibodies isolated from antisera against (Phe,G)-A-L of C3H.SW and C3H/DiSn mice possess part of the idiotypic determinants existing on antibodies of C3H.SW obtained by immunization with (T,G)-A-L. In contrast, antibodies to (Phe,G)-A-L that did not bind (T,G)-A-L did not share idiotypic determinants with C3H.SW antibody molecules against (T,G)-A-L. These results suggest that the B cell repertoire expressed by high and low responders to (T,G)-A-L after immunization with (Phe,G)-A-L is similar and represents only part of that of high responders immunized with (T,G)-A-L.

Animals↗
PubMed1978

Expression of T cell suppressor activity in the immune response of newborn mice to a T-independent synthetic polypeptide.

One and two day old mice responded to the T-independent synthetic polypeptide poly (DTyr,DGlu)-poly(DPro)--poly(DLys) with high antibody production, whereas a dramatic decrease was observed in the immune response of 3 day old injected animals. The presence and expression of suppressor T cells in the 3 day old newborn mice spleens was demonstrated by transferring spleens of 3 day old mice into either thymectomized, irradiated recipients together with bone-marrow cells, or into 1--2 day old newborn recipients. In both cases a significantly lower antibody response was observed in recipients of the 3 day old newborn spleen cells as compared to recipients of the same number of adult spleen cells. No decrease in the antibody levels was detected following inoculation of 3 day old spleen cells after anti-theta-treatment, while enriched T cell populations obtained from nylon wool columns had the same suppressive effect as the whole spleen cell preparations. Thus, the cell expressing the suppressor activity in the newborn spleen is a T cell.

Animals↗
PubMed1978

The mode of interaction with macrophages of two ordered synthetic polypeptides which differ in their thymus dependency.

The mode of interaction with macrophages of two ordered synthetic polypeptides (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, which differ in their requirements for T-B cell co-operation in the process of antibody production, was compared. The binding of the two radiolabelled antigens to the surface of peritoneal adherent cells, their uptake by the cells and the rate of their degradation were investigated. Macrophages were found to be capable of degrading both poly-peptides with the same efficiency. (T-G-T-G)-A--L, the antigen which is less T-dependent, was bound to macrophage surfaces more readily than (T-T-G-G)-A--L, the T-dependent antigen, however, its uptake by the cells was found to be lower. Thus, (T-G-T-G)-A--L remains for a longer period in the form of a membrane bound polyvalent antigen.

Animals↗
PubMed1977

Lymphocytes alloantigens associated with X-chromosome-linked immune response genes.

A new polymorphic alloantigen system controlled by loci on the X-chromosome has been identified by using antisera from F1 hybrid mice differing in their X-chromosome. These alloantigens are associated with the X-chromosome. These alloantigens are associated with the X-linked immune response genes controlling the immune response to the so-called "thymus independent antigens" such as type III pneumococcal polysaccharide, poly(I)-poly(C), and denatured DNA. They also show association with the histocompatibility locus present on the X-chromosome. They were mainly detected on a not yet characterized thymus-derived lymphocyte subpopulation. A certain similarity with the major histocompatibility complex of the mouse supports the possibility of additional I-like regions besides the I region of the histocompatibility-2 complex.

Animals↗
PubMed1977

Antigen-specific T cell factors: a fine analysis of specificity.

The specificity of T cell factors produced in presence of synthetic polypeptide antigens was studied. Factors prepared with either one of the three antigens: poly(Tyr,Glu)-poly(DLALa)--poly(Lys), (T,G)-A--L, poly(Phe,Glu)-poly(DLALa)--poly(Lys), (Phe,G)-A--L, and poly(His,Glu)-poly(DLALa)--poly(Lys), (H,G)-A--L, successfully cooperated with B cells for antibody production to the homologous as well as to the other two immunogens. Furthermore, the activity of a (T,G)-A--L-specific factor was removed after passage through immunoadsorbents built of Sepharose coupled to: (T,G)A--L, (Phe-G)-A--L and poly(Glu)-poly(DLAa)--poly(Lys), (G)-A--L, but not to poly (DLALa)--poly(LLys),A--L. No cross-reactivity was observed between (T,G)-A--L and poly(Tyr,Glu)-poly(Pro)--poly(Lys), (T,G)-Pro--L, at the level of T cell factors, as shown using the above approaches. These results lead to the conclusion that specificity of T cell factors, although not identical, is similar to that of antibodies.

Animals↗
PubMed1977

In vitro studies on H-2 linked unresponsiveness. 1. Normal helper cells to (T,G)-A-L and GAT in low and non-responder mice.

Lymphoid cells from unprimed high responder (C57BL/10) and low responder mice (B10.Br, B10.A, CBA) to (T,G)-A-L and high responder (B10, B10.A) and non-responder (B10.G, DBA/I) mice to GAT can be induced to form antigen specific T-helper cells in vitro under identical culture conditions. The helper cells induced from high and low or non-responder mice appear to be identical in efficiency, antigen concentration requirement for induction and induction kinetics.

Animals↗
PubMed1976

Analysis of the role of different cell types in the genetic regulation of antibody production to the thymus-independent synthetic polypeptide poly (DTyr, DGlu)-poly (DPro)--poly (DLys).

The immune response potential of mice to the thymus-independent synthetic polypeptide poly (DTyr, DGlu)-poly(DPro)--poly(DLys)[D(T,G)-Pro--L] is genetically regulated. The defect in the ability of low responder mice to mount an immune response to this antigen appears to be expressed in their B cell population since the presence of thymocytes, or addition of "educated T cells" or supernatant of T cells after stimulation with the antigen neither enhanced, nor suppressed the level of antibodies produced in both low and high responder mice. Low responsiveness could not be enhanced either by stimulation of macrophages or by injection of poly(A) - poly(U) in contrast to the significant effect of these agents on low responses to the thymus-dependent poly(LTyr, LGlu)-poly(LPro)--poly(LLys) [L(T,G)-Pro--L]. These results suggest that macrophages do not participate in the limiting step, or are not involved at all, in antibody production towards the thymus-independent polypeptide. The antibodies produced in response to D(T,G)-Pro--L were found to be mainly of the 7 S class. T cells are not required for the production of mercaptoethanol resistant antibodies to this immunogen since they were found in intact mice as well as in T cell depleted animals.

Animals↗
PubMed1976

Reconstitution of genetically regulated responses against random and ordered synthetic polypeptides by methylated bovine serum albumin as analyzed by isoelectric focusing.

In previous publications it was shown by avidity measurements, cross-reactivity patterns and genetic analyses, that the tetrapeptide T-T-G-G is the immuno-dominant epitope of the synthetic polypeptide (T, G)-A--L. In the present study this close immunological relationship between the random multichain copolymer (T, G)-A--L and the ordered analogue (T-T-G-G)-A--L is extended by two additional criteria. First, the immune response against (T-T-G-G)-A--L in H-2k nonresponder mouse strains can be reconstituted to high antibody levels by complexing this antigen to methylated bovine serum albumin, as was tested earlier for (T,G)-A--L. The antibodies elicited upon reconstitution in both antigenic systems are directed mainly against the same determinant, T-T-G-G. Second, isoelectric focusing analysis of specific antisera developed with radiolabeled antigen revealed restricted 7 S IgG antibody populations in high responder and reconstituted high and low responder mice. The spectra were found to be of similar complexity in the (T,G)-A--L and in the (T-T-G-G)-A--L system. From these data it was concluded that the repertoires of specific B cells to T-T-G-G are very similar in high and low responder strains, and the defect in the H-2k low responder systems should be located at the level of T-B cell cooperation.

Alanine↗
PubMed1976

In vitro proliferative reactions by lymphocytes from both responder and "low" responder mice to (T,G)-A--L.

In summary (T,G)-A--L can induce specific in vitro lymphoproliferative reactions in LNC from immunized mice. From 3-8 weeks after immunization lymphocytes from responder mice react to a much greater degree than from low responders. These proliferative reactions are not specifically enhanced by supernatants of "educated" T cells. However, 2 to 3 months after immunization the lymphoproliferative response of the low responders rises to the same level as that of responder mice.

Animals↗