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H Binz

Publications and source records attributed to H Binz.

At least 73 records · Page 4Linked to original sources

T cell receptors with allo-major histocompatibility complex specificity from rat and mouse. Similarity of size, plasmin susceptibility, and localization of antigen-binding region.

Antisera specific for the constant part Ctau of T cell receptor molecules in mice and rats have been produced in rabbits by immunization with idiotype-positive rat T cell molecules. Such antisera could be shown to react with the majority of normal T lymphocytes from both rats and mice. Mixed leukocyte culture-activated T blasts displayed a higher percentage of positive cells than concanovalin A- or phytohemaglutinin-induced T blasts. Lipopolysaccharide-induced B blasts were not reactive with the antiserum. Lyt-1-,2+,3+ blasts displayed a significantly brighter straining than the corresponding Lyt-1+,2-,3- blasts. Isolation of the reactive molecules from T cells by immunosorption yielded a 70,000-dalton single chain polypeptide as the dominant group of molecules. Plasmin caused the chain to split into 45,000- and 25,000-dalton polypeptides, with the smaller fragment displaying antigen-binding capacity. Molecules identical in size and plasma degradation patterns were isolated from Lyt-1+,2-3- and 1-,2+,3+ blasts. Preliminary functional data supported the view that the antiserum is directed against the constant region Ctau relevant receptor structures on immunocompetent T lymphocytes.

Animals↗

Induction of specific transplantation tolerance via immunisation with donor-directed idiotype(s).

We have re-explored the efficiency of anti-idiotypic immunisation on the generation of transplantation tolerance to cardiac allografts in the rat. Recipient Lewis rats were immunised using 13 different protocols with different doses of anti-DA or anti-BN idiotype(s) and different adjuvants. Four protocols proved successful. Immunisation with Lewis anti-BN blasts either in complete Freund's adjuvant or in muramyl dipeptide (MDP) prolonged the survival of a congeneic AgB incompatible L.BN cardiac allograft from 6.7 +/- 0.3 to 26.8 +/- 5.1 and to greater than 30 +/- 0.0 days, respectively. Immunisation with Lewis anti-T cell 'receptor' in complete Freund's and in MDP increased the survival of a DA heart allograft in Lewis recipients from 6.0 +/- 0.0 days to 13.2 +/- 0.8 and 10.0 +/- 4.0 days, respectively, indicating that most of the MHC effect was also overcome here. The prolongations of survival were immunologically specific, and accompanied by a specific deletion of the relevant alloantibody response. So far no generation of anti-idiotypic antibody in the immunised recipient has been detected; instead, a successful immunisation seems to be accompanied by the generation of immunising idiotype-directed cytotoxic (T?) lymphocytes in the recipient.

Animals↗

Binding of purified, soluble major histocompatibility complex polypeptide chains onto isolated T-cell receptors. I. Reactivity against allo- and self-determinants.

In this study, we tried to get information about the fine antigen-binding ability of purified, soluble, idiotype-positive T-cell receptor molecules. Lewis anti-DA T-cell receptors were purified from normal Lewis serum by the use of anti-idiotypic immunosorbent and sodium dodecyl sulfate-polyacrylamide gel, and were coupled to cyanogen bromide-activated Sepharose 4B. In parallel, Lewis anti-DA, Lewis anti-BN, and DA anti-Lewis alloantibody immunosorbents were prepared. The major Ag-B chain (44,000 daltons) and the two polypeptide chains (34,000 and 27,000 daltons) of Ia were purified from Lewis, DA, and BN lymphocytes and absorbent on the above-mentioned immunosorbents. We found that the major Ag-B chain as well as the two Ia chains were bound to the alloantibody columns if they were derived from the corresponding allogeneic strain. No retaining ability for self-major histocompatibility complex (MHC) or third-party MHC chains was noted with the alloantibody immunosorbents. When using immunosorbents made up of idiotypic T-cell receptors, only two MHC polypeptides of the relevant allo-MHC type were retained, namely, the Ag-B and the heavy Ia chains. No detectable activity was observed when testing the same column for reactivity against third-party MHC polypeptide chains. However, the Lewis anti-DA T-cell receptors could be shown to display weak, but significant, reactivity toward one Lewis MHC polypeptide chain, that is, the heavy chain of Ia type.

Animals↗

[Lymphocyte membrane receptors mediating recognition of antigens (author's transl)].

The present article summarizes briefly our knowledge of antigen-specific B- and T-lymphocyte receptors. Antigen-specific receptors on mammalian B-lymphocytes are mainly monomeric IgM and IgD consisting of conventional immunoglobulin heavy and light chains. The nature of the T-lymphocyte receptors which can specifically recognize antigens is not yet fully defined but it seems that conventional light chains do not participate in the build up of this receptor. However, T-lymphocytes express two polypeptide chains which bear variable domains sharing idiotypic determinants with the corresponding B-lymphocytes. These Tau chains can bind the corresponding antigen.

Antibody Formation↗

Idiotypic determinants on T-cell subpopulations.

Killer T cells with specificity for major histocompatibility antigens have been shown in mice and rats to display idiotypic receptors allowing the lysis of such cells at the effector phase by anti-idiotypic antibodies and complement. A comparison was made between idiotypes displayed by Lyt-1-2+3+ and Lyt-1+2-3- T blasts, generated in the same mixed leucocyte culture (MLC), across an entire H-2 locus barrier. This was done by absorption of anti-idiotypic antibodies with respective T blasts, followed by estimation of the ability of the absorbed antiserum to inhibit MLC or killer T-cell function. Further, the capacity of Lyt-purified, MLC-generated T blasts to provoke specific unresponsiveness via anti-idiotypic immunity in syngeneic recipients was analyzed. Taken together, the results demonstrate that Lyt-1+2-3- T blasts responsible for the major part of MLC proliferation have distincly different idiotypes from those on the Lyt 1-2+3+ killer T cells. That the idiotypes on the killer T-cell presursors can serve as triggering sites for induction of effector T-cell function was then suggested by experiments with Lyt-1-2+3+-purified, normal T cells as precursor cells in vitro. The fact that autoanti-idiotypic antibodies may circumvent the need for helper Lyt-1+2-3- T cells in the generation of allospecific killer T cells indicates that the former cells may normally function partly via such anti-idiotypic reactions.

Animals↗

Alloantigens derived from stimulator cells and bound onto MLC-activated rat T lymphoblasts.

Rat T lymphocytes were activated in MLC (mixed leucocyte culture) against allogeneic stimulator cells. A few percent of such T blasts could be shown to carry IgM on their surface when a mixture of T and B lymphocytes was used as responder cells. The immunoglobulin was absent when purified T lymphocytes served as responders. A large proportion of MLC T lymphoblasts could be shown to carry stimulator alloantigens on their surface. These antigens were demonstrated (a) by indirect immunofluorescence using anti-stimulator alloantibody and FITC (fluorescein isothiocyanate Isomer I)-labelled F(ab)2 fragments of rabbit anti-rat Ig; (b) by autoradiography after internal labelling of stimulator cells, which showed the transfer of label from stimulator to responder cells. For biochemical analysis T blasts were restimulated with internally labelled allogeneic or syngeneic stimulator cells, and bound radiolabelled stimulator alloantigens were analysed on SDS-PAGE (sodium lauryl sulphate polyacrylamide gel electrophoresis). The results suggest that intact SD antigens with a molecular weight of 45,000 daltons and LD determinants with a molecular weight of 34,000 daltons derived from stimulator cells are found on MLC T blasts. No evidence of binding of the 27,000-dalton Ia chain to T blasts was found. Possible arrangements of these molecules on the responder blasts is discussed.

Animals↗

Representation of heavy but not light chain Ig idiotypes on T cell receptors for alloantigens.

We have analyzed idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants by the use of different anti-idiotypic antibodies. Such antisera were produced in (Lewis X DA) F1 rats against Lewis anti-DA alloantibodies (= B cell product) and Lewis T lymphocyte receptors with the same specificity. We found that B lymphocytes bear unique idiotypic determinants which are not present on the corresponding T lymphocytes. T cell unique (not shared by B lymphocytes) idiotypes were so far not detected. T cells idiotypic determinants which are present on heavy but not light chains of the corresponding alloantibodies.

Animals↗

Recognition of antigens by T lymphocytes.

The present review briefly summarizes our knowledge of antigen-specific B and T lymphocyte receptors. Antigen-specific receptors on mammalian B lymphocytes are mainly monomeric IgM and IgD consisting of conventional immunoglobulin heavy and light chains. The nature of the T lymphocyte receptor which can specifically recognize antigens is not yet fully defined. However, it seems that conventional light chains do not participate in the build up of this receptor, and that the receptor is made up of heavy chains of a new immunoglobulin class which has to be further characterized and which we call Tau-chain. The variable region of the T lymphocyte receptors share idiotypic determinants with the corresponding B lymphocyte receptors. The possible linkage between the T cell idiotypes present on the Tau-chains and molecules which are under the control of genes of the Major Histocompatibility Complex of the species are discussed. In the last part of the review two methods for the induction of specific transplantation tolerance in adult animals are described. These methods are based on the concept that T lymphocytes reactive against alloantigens bear idiotypic determinants against which a specific auto-immune response can be initiated.

Animals↗

[Prolonged renal graft survival induced by blood transfusion (author's transl)].

All renal allotransplants performed at the Cantonal Hospital, Zurich, in 1975 and 1976 were analysed with respect to pre-transplant blood transfusions, excluding secondary transplants, patients on dialysis outside of Switzerland, combined renal and pancreatic transplants, and women with previous pregnancies but without transfusions. Among 72 patients left for analysis there were 16 who had never received any pre-transplant blood transfusion. Their graft survival was much worse (one-year graft survival 36%) than that in patients with previous transfusions (one-year graft survival 70--80%). Patients without previous blood transfusion should, therefore, no longer be admitted for renal transplantation.

Blood Transfusion↗

Induction of specific transplantation immune reactions using anti-idiotypic antibodies.

B and T lymphocytes with reactivity against major histocompatibility antigens are known to express this immune potential via a display on the outer surface of antigen-specific, idiotypic receptors. Here, we show that anti-idiotypic antibodies directed against such receptors may serve as specific triggering agents of the idiotype-positive lymphocytes in the physical absence of foreign histocompatibility antigens. This was shown in vitro using normal or immune spleen T cells where anti-idiotypic antibodies would lead to the selective proliferation and development of antigen-specific cytolytic T cells as determined by short-time 51Cr release assays. Furthermore, purified anti-idiotypic antibodies in adjuvant administered in vivo to normal syngeneic animals could be shown to lead to production of high titers of specific alloantibodies. The present experiments were in most cases carried out using auto-anti-idiotypic antibodies as triggering agents. The present results thus lend further support to the concept that idiotype-anti-idiotype reactions may be normal parts of conventional immune processes with either stimulatory or inhibitory consequences, depending upon the prevailing conditions.

Animals↗

Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. II. An analysis of the effects measured at the cellular and serological levels.

T lymphoblasts specific for foreign histocompatibility antigens and purified via mixed leukocyte culture (MLC) and 1 g velocity sedimentation procedures can be used as autoimmunogen to produce specific immunological unresponsiveness in adult animals. This unresponsiveness is positively correlated to the production of autoanti-idiotypic antibodies in the blast immunized animals and no evidence of coexisting alloimmunity was found. We consider this autoanti-idiotypic immunity to be the specific inducing agent of the immune tolerance. The blast immunization procedure will lead to selective reduction in T-cell reactivity against the relevant alloantigens as measured by MLC, cell-mediated lympholysis, or graft-versus-host assays. However, in individual animals, dichtomy in suppression between two T-cell assays could sometimes be observed indicating elimination of only a select group of idiotypic functionally distinct population of T cells in these blast-immunized animals. Attempts to abrogate already immune animals by the autoblast procedure were successful, in part suggesting the use of the present procedure when trying to induce in accelerated reversion of such immunity.

Animals↗