PubMed Health⌕ Search

Biomedical subjects

E Zisman

Publications and source records attributed to E Zisman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Autoantibodies to prostate specific antigen in patients with benign prostatic hyperplasia.

PURPOSE: We tested for a possible autoimmune process in benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Titers of IgG antibodies to prostate specific antigen (PSA) were measured in the sera of 85 BPH patients, 20 controls and 17 chronic prostatitis patients by enzyme-linked immunosorbent assay. RESULTS: The mean anti-PSA titers in the BPH group were significantly higher than in the controls and prostatitis group (p < 0.0005). Accordingly, 59% of BPH patients could be defined as responders to PSA compared to none among the controls (p < 0.0005). CONCLUSIONS: Circulating autoantibodies to PSA were shown to exist in the sera of BPH patients. This observation suggests that autoimmune processes may have a role in BPH.

Adult↗
PubMed1994

Dichotomy between the T and the B cell epitopes of the synthetic polypeptide (T,G)-A--L.

Studies with the well-characterized, synthetic, random-multichain polypeptide poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) (T,G)-A-L) led to the discovery of determinant-specific genetic control of the immune response, as well as to other immunological phenomena. Moreover, the tetrapeptide TyrTyrGluGlu built on the same backbone ("(T-T-G-G)-A--L") was found to represent its major B cell epitope. We have recently shown that for interaction with major histocompatibility complex class II molecules and stimulation of T cells, (T,G)-A--L requires proteolytic processing and the resulting T cell epitopes are close to the N termini of the branched polymer's side chains. Thus, we were interested to elucidate the major T cell epitope of (T,G)-A--L, by using the ordered polypeptides (T-T-G-G)-A--L and (T-G-T-G)-A--L, in which only the two internal amino acids of the tetrapeptide attached to the side chains are switched. We established T cell lines to these antigens, and found that the ordered analog (T-T-G-G-)-A--L, which was defined as the B cell epitope of (T,G)-A--L, did not represent its T cell epitope, whereas (T-G-T-G)-A--L, to which only a minor anti-(T,G)-A--L Ab response was directed, was found to be its major T cell epitope. In addition, there was no cross-reaction between (T-G-T-G)-A--L and (T-T-G-G)-A--L at the T cell level, similar to the lack of cross-reaction of their antibodies. Analysis of the repertoire of the T cell receptors used by these lines revealed that the (T,G)-A--L and the (T-T-G-G)-A--L specific T cell lines were not restricted in their V alpha and V beta TCR usage, whereas the (T-G-T-G)-A--L-specific line was restricted by both V alpha and V beta T cell receptor gene products. This difference might be due to the thymus-independent characteristics previously described for the latter antigen.

Animals↗
PubMed1994

Processing requirements of two acetylcholine receptor derived peptides for binding to antigen presenting cells and stimulation of murine T cell lines.

We have previously identified two myasthenogenic T cell epitopes of the human acetylcholine receptor (AChR) alpha subunit, peptides p195-212 and p259-271. These peptides were the immunodominant T cell epitopes of AChR in SJL and BALB/c mice respectively, and only cryptic in C3H.SW strain. In order to find out whether these mouse strains differ in their requirements for processing of the same T cell epitopes, we used p195-212 specific T cell lines from SJL, TCSJL195-212, and C3H.SW, TCSW195-212, mice, and p259-271 specific T cell lines from BALB/c, TCBALB/c259-271, and C3H.SW, TCSW259-271, mice. The peptide-specific proliferative responses of the lines TCSW195-212 and TCSW259-271, originated from strains in which these peptides are cryptic epitopes, were inhibited significantly in the presence of several inhibitors of proteases or glutaraldehyde-fixed antigen presenting cells (APC). In contrast, the proliferative responses of the lines TCSJL195-212 and TCBALB/c259-271, established from strains in which these peptides are immunodominant, were only slightly affected by the above inhibitors or by fixation of the APC. Using a direct binding assay of biotinylated peptides to live intact APC, we showed that peptides p195-212 and p259-271 preserved their binding capacity to APC of SJL and BALB/c mice respectively when processing was inhibited. Thus, the AChR peptides that represent cryptic T cell epitopes have to be processed before they can be recognized by T cells, whereas no further processing is necessary for APC presentation and T cell stimulation when these peptides are immunodominant epitopes.

Amino Acid Sequence↗
PubMed1993

Ia-antigen-T-cell interactions for a thymus-independent antigen composed of D amino acids.

Synthetic polypeptide antigens of L amino acids, although bearing repeating sequences, are thymus-dependent (L-TD), whereas the same polymers composed of D amino acids are thymus-independent (D-TI), probably due to a slower rate of metabolism. Yet we found that lymph-node cells of BALB/c mice immunized with D-TI proliferate in response to it in vitro. To follow T-cell activation by D-TI, we established T-cell hybridomas to D-TI and to its analog composed of L isomers, L-TD, for comparison. The T-cell hybridomas express membrane alpha/beta T-cell receptors and secrete interleukin 2 upon stimulation with the respective antigen. In addition, D-TI-specific hybridomas are stimulated, to a lesser extent, by the L-TD antigen, whereas only some L-TD-specific hybridomas recognize D-TI. Moreover, biotinylated analogs of D-TI and L-TD bind to splenic antigen-presenting cells (APCs) from BALB/c mice. Binding is inhibited by an excess of nonbiotinylated L-TD, and by an excess of a peptide comprising residues 259-271 of the human acetylcholine receptor alpha subunit, which binds to I-Ad and I-Ed molecules without prior processing. Analysis of APC lysates following incubation of the APCs with biotinylated D-TI and L-TD reveals that the biotinylated antigen moiety is associated with Ia molecules. D-TI and L-TD bind to Ia molecules on intact APCs with similar KD values, 5 x 10(-8) M and 3 x 10(-8) M, respectively. However, D-TI has faster kinetics of binding than L-TD, probably due to different processing requirements. Hence, we have demonstrated a major histocompatibility complex class II-mediated T-cell response to a thymus-independent antigen.

Amino Acids↗
PubMed1993

Production of colony-stimulating factor 1 by T cells: possible involvement in their interaction with antigen-presenting cells.

Colony-stimulating factor 1 (CSF-1) is required for the growth and differentiation of mononuclear phagocytes, and is also involved in modulating various activities in mature cells. We report herein that T-cell lines produce 4.6 and 1.5 kb mRNA species of CSF-1, and express the CSF-1 protein on their outer membranes, as determined by immunofluorescence staining with anti-CSF-1 antibodies. The CSF-1 protein is biologically active. Interested by the possible immunoregulatory function of CSF-1, we assessed its effect in an assay of antigen presentation to the T cell lines. We found that anti-CSF-1 antibodies inhibited T-cell stimulation. Moreover, soluble CSF-1 could not overcome this inhibition, but exerted a significant inhibitory activity on the interaction between T cells and antigen-presenting cells leading to T-cell activation and proliferation in vitro. Based on these observations we propose that T-cell CSF-1 may be involved in the interaction of these cells with CSF-1 receptor bearing antigen-presenting cells.

Amino Acid Sequence↗
PubMed1992

A tale of two peptides, TyrTyrGluGlu and TyrGluTyrGlu, and their diverse immune behaviour.

Studies on a synthetic multichain polypeptide antigen, (T,G)-A--L, prepared by polymerization techniques, led to a better understanding of the molecular basis of antigenicity, and of many other immunological phenomena, as well as to the discovery of determinant-specific genetic control of immune response. In view of the intensity of studies with this polymer, we were interested in elucidating its major B and T cell epitopes. We investigated two tetrapeptides, TyrTyrGluGlu and TyrGluTyrGlu. Both were attached to multichain branched poly(DLalanine). Even though the two resulting synthetic immunogens are essentially identical in their molecular weight, size, shape and composition, and differ chemically only in the sequence of the tetrapeptide epitopes, the immunological differences observed were profound. Antibodies in the two systems do not cross-react. The major B cell epitope of (T,G)-A--L is TyrTyrGluGlu, whereas the major T cell epitope is TyrGluTyrGlu. The two antigens are under different genetic controls, and differ in their uptake by macrophages. The TyrTyrGluGlu polymer is thymus-dependent, whereas the TyrGluTyrGlu polymer is thymus-independent. Investigation of the two tetrapeptides in their polymeric form, by photochemically induced dynamic nuclear magnetic polarization techniques, shows that they differ strongly in their intra-epitope aromatic interactions. Phenolic groups in TyrGluTyrGlu interact with each other, whereas they are far apart in TyrTyrGluGlu, as seen also in computer-derived models.

Amino Acid Sequence↗
PubMed1991

Direct binding of a synthetic multichain polypeptide to class II major histocompatibility complex molecules on antigen-presenting cells and stimulation of a specific T-cell line require processing of the polypeptide.

T-cell activation involves the recognition of foreign antigens as a complex with self-major histocompatibility complex (MHC) proteins on the surface of antigen-presenting cells (APC). Protein antigens usually require uptake by the APC and processing that results in the generation of peptide fragments. The branched synthetic polypeptide (Tyr, Glu)-Ala--Lys was chosen as a model antigen to follow the processing requirements, leading to T-cell activation. It has been demonstrated, by using fixed APC and various inhibitors of proteases, that (Tyr, Glu)-Ala--Lys has to be processed to stimulate a (Tyr, Glu)-Ala--Lys-specific T-cell line of C3H.SW (H-2b) origin to proliferate. To determine whether processing of (Tyr,Glu)-Ala--Lys is required to allow its association with the MHC class II molecules, biotin was covalently attached to it. Binding of the biotinylated (Tyr,Glu)-Ala--Lys to MHC class II gene products on the surface of intact normal APC was directly detected by phycoerythrin-streptavidin. The specificity of the binding was confirmed by its inhibition with anti-I-Ab antibodies as well as with excess of nonlabeled (Tyr,Glu)-Ala--Lys. Furthermore, introducing several inhibitors of proteases to the binding assay, we could substantiate that the proteolysis of (Tyr,Glu)-Ala--Lys is required to allow association of the resulting peptidyl T-cell epitopes with the MHC class II molecules themselves. The presence of the biotin moiety in the resulting peptides suggests that the T-cell epitopes of (Tyr,Glu)-Ala--Lys contain the N-terminal portion of the side chains of the branched polypeptide. An apparent Kd of 8.05 x 10(-8) M was determined, and optimal binding was detected after 10 hr of incubation with the antigen. The latter phenomenon is not due to slow uptake, since uptake of (Tyr,Glu)-Ala--Lys occurs mainly during the first 30 min of incubation, but rather reflects the events of processing that precede MHC interaction.

Animals↗
PubMed1991

Regulatory T cell activity specific to human type II and III collagens in rheumatoid arthritis.

Fifty-one patients with rheumatoid arthritis (RA) were examined for their immune response potential to human collagen type II and III. It was found that T cells of 57% of patients with RA proliferated to collagen type III whereas only 27% of T cells of patients with osteoarthritis (OA) and healthy controls responded to this antigen by proliferation (p less than 0.04). A lower percentage (38%) of patients with RA had proliferative responses to collagen type II in comparison to 17% of responders in healthy controls. The capability to produce T cell helper factors specific to collagen type III was found to be significantly higher in patients treated with nonsteroidal antiinflammatory drugs (NSAID) (60%) in comparison to patients with OA (16%) and healthy controls (13%). Immunoregulatory drugs affected the specific T helper function in response to collagen type III but did not change the proliferative responses to collagen type II and III in patients with RA. HLA analyses revealed a significant difference in the frequency of HLA-DRw10 between our sample of patients with RA and healthy controls.

Antibody Formation↗
PubMed1989

Direct binding of a myasthenia gravis related epitope to MHC class II molecules on living murine antigen-presenting cells.

MHC gene products present antigenic epitopes to the antigen receptor on T cells. Nevertheless, direct binding of such epitopes to MHC class II proteins on normal living antigen-presenting cells (APCs) has not yet been demonstrated. We have previously shown a significant difference in the ability of T cells of myasthenia gravis (MG) patients to proliferate in response to the synthetic peptide p195-212 of the human acetylcholine receptor (AChR) alpha-subunit in comparison to healthy controls. The observed proliferative responses correlated significantly with HLA-DR5. Moreover, lymph node cells of various mouse strains that were primed with the T cell epitope, p195-212, were found to proliferate to different extents. To investigate these observations further, we designed an assay for direct binding of p195-212 to MHC class II proteins on the surface of freshly prepared splenic adherent cells. Binding of a biotinylated p195-212 was monitored using phycoerythrin-avidin by flow cytometry. Fifteen to sixty per cent of the cells were labeled following incubation with the biotinylated peptide. Binding was observed only to splenic adherent cells derived from mouse strains of which T cells were capable of proliferating in response to p195-212. The binding specificity, in terms of epitope structure and its site of interaction on the cells, was shown by its inhibition with an excess of the unlabeled peptide or with the relevant monoclonal anti-I-A antibodies. These results constitute the first direct evidence for the specific binding of a T cell epitope to live APC.

Amino Acid Sequence↗