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J Ivanyi

Publications and source records attributed to J Ivanyi.

At least 127 records · Page 7Linked to original sources
PubMed1988

Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis.

A serological survey was performed in groups of patients with active sputum smear-positive or smear-negative pulmonary tuberculosis, healthy household contacts, and controls. Sera were tested for titers of antibodies which bound to each of five purified mycobacterial antigens by enzyme immunoassay and for competition of binding to single epitopes, using six radiolabeled monoclonal antibodies directed toward corresponding molecules. The evaluation of diagnostic specificity was based on a positive score represented by titers above the cutoff point of 2 standard deviations above the mean titer of a control group. For smear-positive samples, the best sensitivity (83%) was achieved by exclusive use of the 38-kilodalton (kDa) antigen or its corresponding monoclonal antibodies. For smear-negative samples, levels of antibodies binding to the 19-kDa antigen showed a lower sensitivity of 62% compared with the control group or 38% compared with the contact group. Titers of antibody binding to the 14-kDa antigen were raised in Mycobacterium bovis BCG-vaccinated contacts, indicating that the greatest potential of this antigen may be in the detection of infection in a population for which tuberculin testing is unreliable. The results demonstrated the differing antibody responses to each of the tested antigens and distinct associations with the stage of infection or disease.

Antibodies, Bacterial↗
PubMed1987

T cell activation by anti-idiotypic antibody: mechanism of interaction with antigen-reactive T cells.

It has been shown that the activation of T cells by an anti-idiotypic antibody (anti-Id) TB71 containing an internal image of the corresponding mycobacterial antigen (38 kDa) was achieved by the interaction of anti-Id TB71 with the T cell receptor complex (CD3/Ti). The accessory cell requirement in this response could not be replaced by anti-Id TB71 coupled to Sepharose beads and was not inhibited by Fc receptor blockade. When taken together with the finding that anti-Id TB71-induced proliferation of a T cell clone was restricted by determinants encoded by the major histocompatibility complex, these findings suggested that anti-Id TB71 was presented to 38-kDa antigen-reactive T cells by the same mechanisms as conventional antigenic determinants. That is, both stimulated T cells through the CD3/Ti complex and had to be presented in the context of class II molecules on accessory cells. The finding that the disruption of the integrity of the anti-Id TB71 combining site did not affect T cell responsiveness although antibody binding was ablated implied that anti-Id TB71 may be partially degraded and re-expressed with MHC class II determinants.

Antibodies, Anti-Idiotypic↗
PubMed1987

Mapping of T cell epitopes using recombinant antigens and synthetic peptides.

Two complementary approaches were used to determine the epitope specificity of clonal and polyclonal human T lymphocytes reactive with the 65-kd antigen of Mycobacterium leprae. A recombinant DNA sublibrary constructed from portions of the 65-kd gene was used to map T cell determinants within amino acid sequences 101-146 and 409-526. Independently, potential T cell epitopes within the protein were predicted based on an empirical analysis of specific patterns in the amino acid sequence. Of six peptides that were predicted and subsequently synthesised, two (112-132 and 437-459) were shown to contain human T cell epitopes. This corroborated and refined the results obtained using the recombinant DNA sublibrary. Both of these regions are identical in M. leprae and M. tuberculosis and are distinct from the known B cell epitopes of the 65-kd protein. This combination of recombinant DNA technology and peptide chemistry may prove valuable in analysis of the cellular immune response to infectious agents.

Amino Acid Sequence↗
PubMed1987

Use of anti-idiotypic antibodies as probes for the interaction of TSH subunits with its receptor.

TSH is a heterodimeric glycoprotein hormone, whose dissociated subunits are without biological activity. This has precluded the assessment of the relative contribution of each subunit to hormone action. We have raised anti-idiotypes to monoclonal antibodies specific, respectively, for the alpha and beta hTSH subunits. The anti-beta anti-idiotype inhibited 125I-hTSH binding to the beta subunit-specific monoclonal quantitatively, whereas 125I-hTSH binding to the alpha subunit-specific monoclonal was not inhibited by anti-alpha anti-idiotypes, suggesting that only the former is an "internal image" anti-idiotype. Neither of the two anti-idiotypes nor equimolar mixtures thereof inhibited 125I-bTSH binding to thyroid membranes, even though radiolabelled anti-idiotypes showed saturable binding to thyroid plasma membrane which was inhibited 41-65% by bTSH. Each anti-idiotype alone caused 9% inhibition (compared to 50% by NRIgG) of thyroid plasma membrane adenylate cyclase. Equimolar mixtures (125 micrograms/ml IgG of each anti-idiotype) induced enzyme activity equivalent to 85% of that of 250 mU/ml of TSH. The TSH-like action of the two anti-idiotypes was also reflected in their capacity to increase (450% by 250 micrograms/ml IgG compared to normal rabbit IgG) the uptake of 131I into isolated thyrocytes and to promote the organization of such cells into follicular structures. At 250 micrograms/ml, anti-beta anti-idiotype promoted the organization of small follicles and only at a concentration of 500 micrograms/ml did it enhance 131I uptake.

Animals↗
PubMed1987

Enhancement of bovine growth hormone activity in vivo by monoclonal antibodies.

Monoclonal antibodies (MAbs) prepared against ovine growth hormone (oGH) and recognizing several distinct or related specificities on bovine growth hormone (bGH), have been shown to strikingly enhance the growth promoting properties of the hormone in vivo as determined by 35SO2-4 incorporation in cartilage. The phenomenon is dependent on both hormone and antibody dose and is saturable in the presence of excess antibody. Competition binding analysis between pairs of antibodies has shown that they define distinct antigenic regions on bGH of which one is represented by four MAbs. The most potent growth enhancement was associated with a group of three MAbs (OA11, OA12 and OA13) binding to topographically closely related sites. Another MAb (OA14) with a specificity similar to OA11 and OA13 as defined by competition assay failed to enhance bGH activity. Two antibodies binding to a further two sites (OA15 and OA16) demonstrated modest growth enhancement activity when in complex with bGH, whereas the binding of another antibody (OA17) did not significantly affect hormonal activity. Univalent antibody fragments (Fab) derived from MAb OA11 were equi-potent to the bivalent form of the antibody in the enhancement of bGH activity. Determination of the effects of the different MAbs on the binding of 125I-bGH to liver microsome receptors revealed substantial increase in specific binding (3.5-fold) and is associated with some growth enhancing MAbs. However, not all growth enhancing MAbs increased receptor binding and in the case of one, OA16, clear cut inhibition of receptor binding was observed. Tentative conclusions have been drawn on the possible underlying mechanisms of the MAb mediated enhancement phenomenon.

Animals↗
PubMed1987

Immunopurification of radiolabelled antigens of Mycobacterium leprae and Mycobacterium bovis (bacillus Calmette-Guerin) with monoclonal antibodies.

Radiolabelled sonicate of Mycobacterium leprae when examined by SDS-PAGE and two-dimensional gel electrophoresis (2-DE) contained fewer antigens than the comparable sonicate from M. Bovis (bacillus Calmette-Guerin) (BCG). A solid-phase immunopurification assay with anti-M. leprae monoclonal antibodies (MoAb) was used to characterize four of these antigens. Three of the MoAb were M. leprae-specific and with them antigens with apparent molecular weights (Mr) of 12,000 (12K), 18K, and 35K were isolated. On 2-DE, the heavily labelled 12K antigen was heterogeneous with a range in pI of 4.8-5.2. The 35K antigen, which was identified by a conformational determinant, and the 18K antigen were also acidic proteins with pI of 5.4 and 5.1. The fourth antigen was purified from both M. leprae and BCG sonicates and had an Mr of 70K and a pI of 5.1. MoAb reacting with the cell wall protein of M. leprae resulted in separation of multiple bands ranging in Mr from 12K to 65K, rather than the dominant 65K protein seen in immunoblots. A similar pattern was obtained with MoAb that reacted with two cell wall polysaccharide antigens, and these antibodies may have co-precipitated the radiolabelled cell wall proteins. Immunoprecipitates of the M. leprae sonicate with human lepromatous leprosy sera, when analysed by 2-DE, were also found to contain the dominant 12K band and the 35K band. Furthermore, half the radiolabelled BCG antigens were precipitated by the same sera.

Antibodies, Bacterial↗
PubMed1987

Characterization of antibody-reactive epitopes on the 65-kilodalton protein of Mycobacterium leprae.

Twenty-three monoclonal antibodies (MAbs) prepared in seven different laboratories were studied, all of which recognized the 65-kilodalton (kDa) protein of Mycobacterium leprae as determined by Western blotting or gel radioimmunoassay or both. Fourteen of the MAbs recognized different epitopes, as evaluated by cross-competition studies using radiolabeled MAb and unlabeled inhibitors; the species specificity of these epitopes was defined by nitrocellulose dot blot immunoassays with bacterial sonic extract antigen preparations from 23 species of mycobacteria. Each of the 14 distinct MAbs recognized a 65-kDa protein produced by a lysogenized Escherichia coli Y1089 host containing cloned rDNA which included the gene for the M. leprae 65-kDa protein. Of the 14 distinct MAbs, 1 recognized an epitope found only on M. leprae, and the others recognized epitopes present on as few as 8 or as many as all 23 of the mycobacterial species studied. Identification of these distinct 65-kDa protein epitopes and use of the MAbs which recognize them should assist future structural studies of this protein and characterization of the T-cell reactive and serodiagnostically useful portions of the molecule.

Antibodies, Monoclonal↗
PubMed1987

Monoclonal antibodies can enhance the biological activity of thyrotropin.

In this work we demonstrate that monoclonal antibodies (MABs) to TSH can enhance the biological actions of TSH in vivo. Hypopituitary Snell dwarf mice were injected with TSH (25, 50, or 100 mU/day) alone or complexed with MAB-GC73 once per day for 5 days; control animals received PBS. Radioactive sulfate (35SO4(2-)) was also injected on the fifth day and animals were killed 20 h later. Thyroids were removed for histology, blood taken for T4 estimations by RIA, and 35SO4(2-) uptake into costal cartilage in vivo was measured. In control mice thyroid histology revealed small follicles comprised of small flattened epithelial cells with a high nuclear-cytoplasmic ratio; colloid was dark with little vacuolation. In animals treated with TSH alone there was moderate evidence of activation in most of these features. However, a marked response was noted in animals treated with TSH plus MAB-GC73; characteristically, there was little interfollicular tissue and the follicles, which were large and comprised of cuboidal cells, contained pale, finely vacuolated cytoplasm. Both TSH alone and TSH complexed with MAB-GC73 promoted a significant dose-dependent increase in serum T4 levels. The two higher doses of TSH plus MAB-GC73 promoted a significantly greater increase in serum levels of T4 than that in groups receiving the same dose of TSH alone. Uptake of 35SO4(2-) into costal cartilage showed a significant correlation with serum T4 levels. In similar experiments significant increases in salivary gland epidermal growth factor content of male dwarf mice were observed. This work demonstrated that MAB enhancement of hormone action is not restricted to human GH, suggesting a more general phenomenon.

Animals↗
PubMed1987

T-cell activation by anti-idiotypic antibody: evidence for the internal image.

Human lymphoproliferative responses to a rabbit anti-idiotypic antibody (anti-Id TB71) and the corresponding mycobacterial protein antigen [38,000 molecular weight (MW)] have been investigated in a number of donors. It was found that responsiveness to anti-Id TB71 correlated with responder and non-responder (four subjects each) status to the 38,000 MW antigen. Furthermore, the induction of T-cell proliferation by both the 38,000 MW antigen and the anti-Id TB71 was dependent on accessory cells. When taken together with the concordance between the 38,000 MW antigen and anti-Id responsiveness, this implies that the 38,000 MW antigen and anti-Id TB71 stimulate related, or at least partially overlapping, repertoires of T cells. This was confirmed by the finding that cloned T cells reactive with the 38,000 MW antigen also proliferated in response to the anti-Id TB71. These observations are readily explained if the anti-idiotypic antibody contains an internal image of, and can therefore mimic, the antigen.

Animals↗
PubMed1987

Stimulation by anti-idiotype antibody of murine T cell responses to the 38 kD antigen of Mycobacterium tuberculosis.

Rabbit antisera raised against eight monoclonal antibodies (MoAb) binding to distinct mycobacterial antigens revealed individual anti-idiotype specificities following cross-absorption with normal mouse globulin. Only one of these antibodies (Rb71), directed towards an M. tuberculosis-specific epitope on the 38 kD protein antigen was able to stimulate mouse T cell responses which had 'internal image' characteristics. This was demonstrated by anti-Id induced in vitro proliferation of Lyt 1.2+ T cells and the elicitation of delayed type hypersensitivity (DTH) foot pad reactions in antigen stimulated BALB/c mice. The DTH reaction was equally strong in mice sensitized with either M. tuberculosis or M. bovis soluble extracts, thus showing a greater degree of cross-reactivity than antibody binding of the corresponding TB71 MoAb. The immunizing potency of the anti-Id in vivo was demonstrable in three strains of mice following injection of Rb71 emulsified with incomplete Freund's adjuvant. These mice showed 38 kD antigen induced DTH-reactions as well as in vitro proliferation of spleen cells. The display of T cell stimulatory internal image by anti-Id may be interpreted as a consequence of binding specificity of TB71 MoAb of a T cell epitope present in the 38 kD antigen.

Animals↗
PubMed1987

Suppression of delayed hypersensitivity skin reactions to tuberculin by M. leprae antigens in patients with lepromatous and tuberculoid leprosy.

Delayed hypersensitivity skin reactions to tuberculin when injected alone or in mixture with antigens of M. leprae were examined in leprosy patients and in healthy controls. The tuberculin reaction was significantly inhibited in more than one half of both LL and BT patients by the soluble extract of M. leprae (leprosin), the leprosin derived 12 kD protein or leprosin depleted of the 12 kD antigen. However, suppression was not found in healthy controls from a leprosy endemic region. These results suggest that multiple M. leprae-specific antigens have an immunoregulatory function. Since suppression was demonstrable not only in LL (leprosin-anergic), but also in BT (leprosin-responder) patients it is of interest that the 'mixed' skin test can discriminate the immune status of at least certain BT patients from that of the infected but self-healing healthy controls. Corollary lymphocyte cultures failed to show any suppression by leprosing of the lymphoproliferative responses to tuberculin.

Antigens, Bacterial↗
PubMed1987

Study of idiotypes expressed by monoclonal antibodies to the 35 kD and 12 kD antigens of Mycobacterium leprae.

Rabbit antisera were raised against four monoclonal antibodies (MoAb) binding with the 35 kD protein and four MoAb binding with the 12 kD protein antigen of Mycobacterium leprae. Antisera showed idiotype (Id) specificity following cross-absorption with normal mouse globulin. One Id on a single MoAb and another Id shared between three MoAb were identified for each group. Functional studies were carried out with the Rb04 anti [anti-35 kD] specificity. The expression of this Id and paratope in antigen immunized mice was associated with Igh alleles. Inoculation of mice with anti-Id Rb04 induced an 'Ab3' serum response of corresponding Id specificity only when the anti-Id was given in emulsion with incomplete Freund's adjuvant (IFA). Conversely, prior injection of soluble anti-Id inhibited the subsequent Ab3 response to Rb04/IFA. Moreover, the suppressive effect of soluble anti-Id was abrogated by prior injection of 50 mg/kg cyclophosphamide. These results indicate that regulatory mechanisms similar to those involved in antigenic stimulation may explain the stimulatory or suppressive potency of anti-Id antibodies. Finally, the Ab3 responses to the two tested anti-Ids did not contain any antigen binding activity.

Animals↗
PubMed1986

Split tolerance induced by chick embryo thymic epithelium allografted to embryonic recipients.

To test the capacity of the epithelial component of the chick embryo thymus to induce tolerance to major histocompatibility complex (MHC) antigens, pre-colonized thymic rudiments were grafted into chick embryonic recipients. Semi-allogeneic or allogeneic transplantations were done between two lines of chickens histocompatible at the MHC locus. Approximately 10% of these thymic chimeras hatched and were studied 3 mo after hatching. Thymic grafts were not rejected by the allogeneic host. The tolerance of chimeric chickens to thymus donor MHC antigens was tested by using a skin graft rejection test and a graft-vs-host (GvH) assay. Chimeric chickens that received an MHC-incompatible thymic graft during the embryonic life tolerated skin graft with the MHC haplotype of the thymus donor. Nevertheless, the lymphocytes within the thymic graft, the host thymus, and the blood were tolerant to the host MHC antigens but were alloreactive in GvH reaction for the MHC antigens of the thymic graft type. These results suggest that the epithelial component of the thymus when taken before the starting of the colonization by hemopoietic precursors and grafted into an early chick embryonic host can induce a tolerance for the MHC determinants involved in allograft rejection but not in the GvH reaction.

Animals↗
PubMed1986

Antigen presentation by human monocytes: effects of modifying major histocompatibility complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids.

Lymphocyte proliferation in response to monocytes pulsed with an antigenic extract of Candida albicans was measured in vitro and the effects of modifying major histocompatibility complex (MHC) class II antigen expression at the surface of the antigen-presenting cells was investigated. The study shows that no simple correlation exists between changes in MHC class II antigen expression and changes in the effectiveness of antigen presentation. Recombinant interferon-alpha 1 (rIFN-alpha 1), rIFN-gamma and hydrocortisone were found to increase the expression of monocyte class II MHC antigens. In contrast, rIFN-alpha 2 did not increase class II antigen expression although it did increase MHC class I expression. Treatment of monocytes with rIFN-alpha 1, rIFN-alpha 2 or corticosteroids during antigen pulsing resulted in a reduction in the subsequent proliferative lymphocyte response. In all cases this inhibitory effect was restricted to antigen-specific proliferative responses since the polyclonal lymphocyte response to pokeweed mitogen-pulsed monocytes remained unaffected. Only rIFN-gamma treatment of antigen-pulsed monocytes resulted in enhancement of the subsequent specific lymphocyte proliferative response. The suppressive effects of hydrocortisone could not be attributed to its well documented inhibitory effects on arachidonic acid metabolism. The effect of C. albicans antigen, IFN and corticosteroids on interleukin 1 (IL 1) production by monocytes was also investigated. C. albicans antigen alone induced IL 1 production. So too did IFN-alpha 1 and IFN-gamma. IFN-alpha 2 did not induce IL 1 production. Addition of interferons together with C. albicans, however, resulted in the same level of IL 1 productions as with C. albicans antigen alone. Neither antigen nor IFN had any effect on IL 1 action in the thymocyte assay. Corticosteroids did not affect IL 1 production by monocytes but were potent antagonists of IL 1 in the thymocyte proliferation assay. Mitogen-induced thymocyte proliferation was also inhibited by corticosteroids. Pretreatment of monocytes with hydrocortisone followed by washing did not markedly affect their subsequent ability to produce IL 1 neither was it possible to reverse the inhibitory effects of hydrocortisone on antigen presentation by addition of exogenous IL 1. Thus, signals which alter class II MHC antigen expression influence the antigen-presenting capacity of monocytes by a mechanism independent of IL 1. No simple correlation exists between class II expression and antigen-presenting capacity.

Adrenal Cortex Hormones↗
PubMed1986

Epitope specificity of blood-group-A-reactive murine monoclonal antibodies.

Monoclonal antibodies (MABs) towards blood groups A manifested three broad patterns of binding distinguished on the basis of affinities for A1 or A2B phenotype red blood cells and blood group substances. Competitive inhibition of binding of radiolabelled MABs by other unlabelled antibodies and absorption studies with synthetic haptens suggested that GpA specificity was expressed as two topographically related structures, one being the terminal GpA trisaccharide and the second probably involving part of the oligosaccharide backbone. The enhancement of binding of an extremely low-affinity antibody by higher affinity antibodies recognising either epitope indicated a topographic, possibly conformational relationship between these epitopes. It is suggested that only those antibodies that recognise terminal GpA trisaccharides can agglutinate weak A2B cells.

ABO Blood-Group System↗