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T R Mosmann

Publications and source records attributed to T R Mosmann.

At least 91 records · Page 5Linked to original sources
PubMed1987

Species-specificity of T cell stimulating activities of IL 2 and BSF-1 (IL 4): comparison of normal and recombinant, mouse and human IL 2 and BSF-1 (IL 4).

Mouse and human interleukin 2 (IL 2) both cause proliferation of T cells of the homologous species at high efficiency. Human IL 2 also stimulates proliferation of mouse T cells at similar concentrations, whereas mouse IL 2 stimulates human T cells at a lower (sixfold to 170-fold) efficiency. In contrast, the T cell stimulating activities of mouse and human B cell stimulatory factor 1 (interleukin 4; IL 4) appear to be species specific over the range of concentrations tested; we detected no activity of mouse IL 4 on human T cells, or human IL 4 on mouse T cells.

Animals↗
PubMed1986

Alterations in the amino-terminal third of mouse interleukin 2: effects on biological activity and immunoreactivity.

In this report, we describe plasmids that direct the expression of active mouse interleukin 2 (mIL 2) in Escherichia coli, and the use of this expression system to perform a mutational analysis of the N-terminal region of the mIL 2 protein. We found that the N-terminus was tolerant to the addition of a few amino acids, and even the addition of 20 amino acids resulted in only a modest decrease in activity of the protein. The bioactivity of mIL 2 as defined by its ability to sustain the proliferation of cloned T cells was also only minimally affected by deletion of up to 13 N-terminal amino acids, or of the entire poly-GLN stretch (amino acids 15-26). Deletion of the 30 N-terminal amino acids drastically reduced but did not abolish activity. Deletion of the 41 N-terminal amino acids completely abolished activity, whereas certain changes in the initial 37 amino acids drastically reduced the biological activity of the protein. We also analyzed the immunoreactivity of the mutant proteins with the anti-IL 2 monoclonal antibodies S4B6 and DMS-1. This analysis showed that the determinant recognized by S4B6 required that the N-terminal mIL 2 amino acids 26-45 be intact, whereas the DMS-1 determinant was located to the C-terminal side of amino acid 46.

Amino Acid Sequence↗
PubMed1986

Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Clones representing each type of T cell were characterized, and the pattern of lymphokine activities was consistent within each set. The secreted proteins induced by Con A were analyzed by biosynthetic labeling and SDS gel electrophoresis, and significant differences were seen between the two groups of T cell line. Both types of T cell grew in response to alternating cycles of antigen stimulation, followed by growth in IL 2-containing medium. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+, Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and KLH. The relationship between these two types of T cells and previously described subsets of T helper cells is discussed.

Animals↗
PubMed1986

Murine T-cell clones specific for chicken erythrocyte alloantigens.

We have established murine T-cell clones which respond to allotypic and species-specific determinants found on chicken erythrocytes (cRBC). Their relative antigen specificities were determined by assessing lymphokine production and proliferation in response to syngeneic spleen cells and cRBC obtained from chickens homozygous for major histocompatibility complex (MHC) antigens. The specificity pattern suggested that the T-cell clones recognized a more restricted set of cRBC MHC-associated allodeterminants than do antibody-producing cells. The antigen-specific responses required antigen processing, and were MHC restricted and antigen dose dependent. Approximately 20% of T-cell clones from appropriate strains of mice were also Mls alloreactive. This second reactivity showed no correlation with nominal cRBC specificity. The induction-specific lymphokine activities of T-cell growth factor, mast cell growth factor, and Ia induction factor were identified as interleukin 2 (IL-2), interleukin 3 (IL-3), and interferon-gamma respectively.

Animals↗
PubMed1986

T-cell and mast cell lines respond to B-cell stimulatory factor 1.

The murine lymphokine B-cell stimulatory factor 1 (BSF-1) has been described previously in terms of its action on B lymphocytes. We now provide evidence that BSF-1 is also responsible for two additional biological activities. The first of these is the stimulation or maintenance of a state of activation in mouse T-cell lines. The second activity is the increase in the proliferative rate of certain mast cell lines costimulated with interleukin 3. The T-cell and mast cell activities are mediated by purified BSF-1 and copurify with BSF-1 from supernatants of certain T-cell lines. Each of these activities is inhibited by monoclonal anti-BSF-1 but not by monoclonal anti-interleukin 2 antibody. The antibody inhibition results also indicate that BSF-1 is the major or only source of these two activities in the activated T-cell supernatants that we have tested.

Animals↗
PubMed1985

Production and characterization of monoclonal antibodies to bovine skin proteodermatan sulfate.

To study the molecular structure and function of bovine skin proteodermatan sulfate, on a determinant by determinant basis, several monoclonal antibodies to this molecule have been produced and characterized. Based on the results of a preliminary immunogenetic analysis of 4 inbred mouse strains, SJL/J (H-2s) mice were immunized for the fusions. Ten hybridomas were produced and the monoclonal antibodies from four of these were selected for further investigation. Employing an ELISA inhibition assay, none showed any detectable affinity for bovine collagen types I, II, III, or IV, bovine fibronectin or chondroitin or dermatan sulfate glycosaminoglycans. Each monoclonal antibody bound the chondroitinase ABC-derived protein core and none was significantly inhibited by proteinase digests of the intact molecule suggesting that the epitope of each contains a protein component. The results of competitive binding ELISA assays and immunoblots of the cyanogen bromide cleavage products of proteodermatan sulfate indicate that the 4 antibodies recognize at least 3 distinct antigenic determinants on this molecule. Immunohistochemical methods located the antigen in the dermis of bovine skin and revealed that a change in proteodermatan sulfate distribution occurs during skin development.

Animals↗
PubMed1983

Post-translational fate of variant MOPC 315 lambda chains in Xenopus oocytes and mouse myeloma cells.

The post-translational fates of three immunoglobulin lambda chain variants of MOPC 315 were investigated in mouse plasmacytoma cell lines and in mRNA-microinjected Xenopus oocytes. Quite unexpectedly we found that one non-secretory variant chain (lambda-43) underwent extensive post-translational N-glycosylation: however the presence of the oligosaccharide moiety did not account for the nonsecretory phenotype nor did it affect the rate of degradation of this lambda chain. Another variant chain (lambda-47) at first believed to be non-secretory, was found to be secreted from oocytes at a very low level, but mostly as a lambda-lambda dimer. In myeloma cells a low level of lambda-47 chain was secreted and again lambda-lambda dimers were the favoured secretory form. The secretory lambda-48 chain also formed lambda-lambda dimers, whereas lambda-43, which was never secreted, was only found as a monomeric lambda chain in both oocytes and myeloma cells. A similar relationship between assembly and secretion was found when oocytes were coinjected with MOPC 21 heavy (gamma 1) chain mRNA and MOPC 315 lambda chain mRNAs. The wild type lambda chain (lambda-48) was able to assemble with the gamma chain in a covalently bound tetramer (gamma gamma lambda lambda). The variant lambda-47 chain was also able to form gamma gamma lambda lambda tetramers, whereas the lambda-43 was not, even when glycosylation was prevented by tunicamycin. Both types of tetramer were secreted. These data reinforce the idea that conformational changes play a major role in the routing of secretory proteins and that the cellular mechanisms by which these changes are recognized are not cell-type specific.

Animals↗
PubMed1982

Specificity of autoimmune monoclonal Fab fragments binding to single-stranded deoxyribonucleic acid.

Fab fragments from hybridoma HEd 10 [Lee, J. S., Lewis, J.R., Morgan, A.R., Mosmann, T.R., & Singh, B. (1981) Nucleic Acids Res. 9, 1707-1721] were prepared in large amounts by papain digestion of the immunoglobulin G (IgG) fraction from ascites fluid. Binding data were generated by a fluorescence quenching technique, and binding constants [K(0)] were estimated from Scatchard plots. The Fab fragments bound tightly to poly(dT) [K(0) = 12.7 X 10(6) M-1], and analysis of binding constants for the series p(dT)2 to p(dT)17 showed that the recognition sequence consisted of four consecutive residues. The effect of ionic strength on the interaction suggested that only two phosphates were involved. Binding constants for poly(dU), poly[d(brU)], poly[d(brC)], and poly(rU) were 1.0 X 10(6) M-1, 18.8 X 10(6) M-1, 0.5 X 10(6) M-1, and less than 0.5 X 10(6) M-1, respectively, implicating the involvement of the 3, 4, and 5 positions of the pyrimidine ring as well as the deoxyribose sugar in the recognition process. At high ionic strength (0.5 M) K(0) for whole IgG binding to poly(dT) was 75 X 10(6) M-1 compared to a value of 1.1 X 10(6) M-1 for the Fab fragment. These results may have implications for the tissue damage caused by DNA-containing immune complexes in systemic lupus erythematosus.

Animals↗
PubMed1982

The high background immune reactivity of mice to polymorphic determinants on xenogeneic erythrocytes: theoretical and practical implications.

Background responses have been assessed by fusing lipopolysaccharide- (LPS) stimulated spleen cells from unimmunized mice with MOPC 315.43 myeloma cells and screening the hybrids for the production of antibody against chicken red blood cells (CRBC). Clones specific for CRBC represented about 1% of total hybrid clones (1000 to 5000 clones were obtained per mouse). The majority of the anti-CRBC clones (greater than 95%) secreted antibody against polymorphic CRBC determinants (present on CRBC from some but not all chickens) rather than species-specific determinants present on all CRBC. Some of the polymorphic determinants were linked to the B locus (the MHC of the chicken) and some were non-B antigens. The relative amount of these 2 categories varied slightly according to the mouse strain. These results agree well with the specificities of natural mouse antibody and rosette-forming spleen cells. The response of immunized mice against CRBC and human RBC was also selective for polymorphic determinants. These results have considerable importance for the use of xenogeneic RBC as "standard" antigens, and are interpreted in terms of a model for the advantages of genetic polymorphism as a protection against antigen mimicry by parasites.

Animals↗
PubMed1982

Preference of the early murine immune response for polymorphic determinants on human lymphoid-leukemia cells and the potential use of monoclonal antibodies to these determinants in leukemia-typing panel.

28 monoclonal antibodies (MCAs) which were produced following immunization of mice with human lymphoid leukemia or lymphoma cells were subjected to extensive specificity testing using immunofluorescence and complement-mediated cytotoxicity assays. All except one of the MCAs reacted with lymphocytes from at least one normal donor, but only 36% reacted with at least one subpopulation of lymphocytes from every normal donor tested. 60% of the MCAs detected polymorphic determinants, the frequency of polymorphism ranging from 27 to 91%, 50% of these MCAs reacting with B lymphocytes but not T lymphocytes. The marked heterogeneity observed when testing human lymphoid leukemias with these MCAs could be explained by both polymorphism and heterogeneity in lymphocyte differentiation marker expression. An awareness of the preferential murine immune response to polymorphic determinants on human lymphoid leukemia cells is essential when interpreting unexpected positive or negative results when testing with MCAs. An MCA believed to be detecting a monomorphic determinant may be detecting a high-frequency (supratypic) polymorphic determinant, and a putative leukemia-specific MCA may be detecting a low-frequency polymorphic determinant. Our panel, which includes MCAs which detect polymorphic determinants, appears useful in following the course of leukemia and may be useful for leukemia classification.

Animals↗
PubMed1981

Monoclonal antibodies showing sequence specificity in their interaction with single-stranded DNAs.

Six hybridoma cell lines which secrete monoclonal antibodies binding to nucleic acids were produced from autoimmune NZB/NZW mice. Four of the antibodies were IgG's and the other two were IgM's. Using a solid phase radioimmunoassay (SPRIA) the binding of the antibodies to over thirty different nucleic acids was estimated. All the antibodies were extremely specific. There was no detectable interaction with various RNAs, and single-stranded DNAs bound more antibodies than duplex or multi-stranded DNAs. In every case the antibodies also showed considerable sequence preferences. For example one monoclonal antibody bound to d(TTC)n but not to d(TCC)n while another interacted strongly with D(TG)n and d(CA)n but not with d(TC)n, d(GA)n or homopolymers. In other cases the patterns of sequence specificity were extremely difficult to interpret although it seems clear that monoclonal antibodies have the potential to distinguish between any two nucleic acids however similar.

Animals↗
PubMed1981

Translation of lymphocyte mRNA into biologically-active Interleukin 2 in oocytes.

A variant line of murine T lymphoma EL4 produces high levels of the lymphokine Interleukin 2 (IL 2) when it is stimulated with phorbol myristate acetate. We have extracted poly A+ RNA from the stimulated cells and injected it into Xenopus laevis oocytes. The injected oocytes synthesize a material with biologic and biochemical properties of murine IL 2. Namely, it stimulates the continued growth of a cloned, cytotoxic T cell line (the T cell growth factor assay) and it chromatographs on a gel filtration column (G-100) with IL 2 produced by the stimulated EL4 line. The RNA responsible for the biologic activity sediments with markers of 11 to 12S in a sucrose gradient. The IL 2 produced by injected oocytes from a given preparation of mRNA is about 1% of the amount produced by the EL4 cells stimulated originally with phorbol myristate acetate. When RNA is extracted and purified from unstimulated EL4 cells it does not induce IL 2 production in oocytes. We conclude that IL 2 is essentially protein in nature, that the protein is coded for by poly A+ mRNA, and that the amount of this mRNA increases significantly after stimulation of the variant EL4 cells with the inducer phorbol myristate acetate.

Animals↗
PubMed1980

Restricted expression of an MHC alloantigen in cells of the erythroid series: a specific marker for erythroid differentiation.

The spectrum of reactivity with various types of cells of a monoclonal antibody (CH-4) which detects a private MHC antigen of chickens was analysed. CH-4 agglutinates only RBCs that possess the B2 (MHC) haplotype. A new rosette-forming cell (RFC) assay was devised to detect individual cells (excluding RBCs) that possess the CH-4 specificity on their cell surfaces. RBCs that have CH-4 chemically coupled to their surfaces attach to, and form rosettes with, B2 antigen-bearing cells. Most non-RBC RFC were detected in active erythropoietic organs (adult bone marrow and embryonic spleen), and none were found in organs where erythropoiesis does not occur: adult thymus and bursa. Preincubation of bone marrow cells with CH-4 plus complement almost completely inhibits their capacity to form CFU-E without affecting their ability to form GM-CFU. In addition, CH-4 plus complement does not inhibit the capacity of B2/B2 lymphocytes to induce a graft-versus-host reaction under conditions where anti-B2 lymphocyte alloantisera are completely inhibitory. Our results strongly suggest that CH-4 monoclonal antibodies detect a private specificity on a gene product of the B-G locus whose expression is restricted to erythroid stem cells and erythrocytes.

Adult↗
PubMed1980

"Natural" antibodies to chicken MHC antigens are present in mice, rats, humans, alligators and allogeneic chickens.

In the absence of any deliberate immunization, mice, rats, humans and alligators all have detectable titers of antibody against chicken red blood cells (CRBC's). Remarkably, this antibody is directed predominantly against private or public determinants of MHC proteins on the CRBC's, and little or no antibody is directed against species-specific determinants on MHC or other proteins, including other polymorphic blood group antigens. In chickens, "natural" antibody can be detected against CRBC's from all chickens differing at the MHC locus, but "natural" antibodies against other polymorphic antigens are not detected. Using a rosette-forming cell (RFC) assay, we have also shown that a large percentage of mouse spleen cells will rosette with chicken erythrocytes, and that the majority of these RFC's also recognize polymorphic antigens.

Alligators and Crocodiles↗