bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted antigen presentation using crosslinked antibody heteroaggregates.
Authors: Snider D P , Segal D M 
Published: December 2022

Abstract
We have targeted protein antigens to antigen-presenting cells in vitro by using antibody heteroaggregates containing an antibody against a protein antigen covalently crosslinked to an antibody against a target structure on the surface of the antigen-presenting cells. Antigen presentation was assessed by measurement of lymphokine released by antigen-specific T cell hybridomas. Depending on the experimental conditions, the crosslinked antibodies decreased the amount of antigen required to give a response by the hybridomas by factors of 10(2) to 10(3). Enhanced presentation occurred when antigen was targeted to MHC class I and class II molecules, surface immunoglobulin, or Fc gamma receptors on the surface of the murine B cell lymphoma-hybridoma, TA3. An enhancement of antigen presentation also occurred when antigen was targeted to surface IgD, or class I and class II MHC molecules on murine splenic B cells, and when antigen was targeted to class I and class II molecules on irradiated adherent spleen cells. No response was seen when antigen was targeted to Fc gamma R on B cells or adherent spleen cells. The ability of each crosslinked antibody to enhance presentation paralleled the total amount of each that bound to the surface of the antigen-presenting cells. Antigen presentation, mediated by crosslinked antibody, was antigen-specific and I-A restricted. The presentation of one antigen by using crosslinked antibody did not result in enhanced presentation of a second, bystander antigen. These results suggest that a novel means of stimulating immune responses may be possible in vivo, by targeting antigen to surface structures on antigen-presenting cells.
Monoclonal antibodies that recognize lacto-N-fucopentaose III (CD15) react with the adhesion-promoting glycoprotein family (LFA-1/HMac-1/gp 150,95) and CR1 on human neutrophils.
Authors: Skubitz K M , Snook R W 
Published: December 2022

Abstract
A variety of monoclonal antibodies has been used to study the roles of surface proteins in neutrophil function. Many monoclonal antibodies that bind to human neutrophils react with the oligosaccharide lacto-N-fucopentaose III. Sequential immunoprecipitation of radiolabeled proteins from extracts of neutrophils labeled at the cell surface with 125I, and partial proteolysis peptide mapping studies were used to compare the proteins recognized by several widely used monoclonal antibodies that react with human neutrophils. The monoclonal antibodies that react with lacto-N-fucopentaose III (CD15) immunoprecipitated five distinct neutrophil surface proteins. The data indicate that CD15 monoclonal antibodies react with a subset of the LFA-1/HMac-1/gp 150,95 glycoprotein family as well as with CR1 on human neutrophils. The CD15 antibodies studied differed in their avidities for these proteins. The molecules immunoprecipitated by the CD15 antibodies tested were more resistant to proteolysis than the homologous proteins immunoprecipitated by the other monoclonal antibodies studied that react directly with the alpha M (CD11) or beta (CD18) chains of the LFA-1/HMac-1/gp 150,95 glycoprotein family. Some of the differences in antibody reactivity and protease sensitivity of the membrane proteins recognized by these antibodies may be due to differences in glycosylation. The data suggest that the antibodies studied can detect differences in post-translational modification among copies of certain surface proteins.
Antigenic analysis of the repeat domain of the circumsporozoite protein of Plasmodium vivax.
Authors: Romero P , Heimer E P , Herrera S , Felix A M , Nussenzweig R S , Zavala F 
Published: December 2022

Abstract
In the present study we analyzed the fine specificity of mouse monoclonal and human polyclonal antibodies directed against the repeat domain of the circumsporozoite (CS) protein of the human malaria parasite, Plasmodium vivax. Five synthetic peptides, representing monomeric and dimeric repeats of this malarial antigen, were assayed for their capacity to inhibit the binding of these antibodies to a yeast-derived recombinant CS protein. The results revealed the existence of at least two distinct repeated overlapping epitopes in the CS protein of P. vivax. Furthermore, polyclonal sera contain antibodies which recognize additional determinants not represented by the synthetic repeat peptides. Some of these sera contain antibodies recognizing a region flanking the repeat domain (region I). The present findings are in contrast with the antibody response in rodents and humans to the Plasmodium falciparum CS protein, which is directed against a single repeated immunodominant epitope.
Stimulation of T lymphocyte proliferation by monoclonal antibodies against GD3 ganglioside.
Authors: Welte K , Miller G , Chapman P B , Yuasa H , Natoli E , Kunicka J E , Cordon-Cardo C , Buhrer C , Old L J , Houghton A N 
Published: December 2022

Abstract
Cell-surface gangliosides are presumed to play a role in cell growth and differentiation. With the use of monoclonal antibodies directed against GD3, a disialoganglioside expressed predominantly by cells of neuroectodermal origin, we have found that GD3 is expressed by a subpopulation of cells of the immune system including: 1) fetal thymocytes in subcortical regions and near vessels, 2) lymph node lymphocytes in interfollicular areas and near vessels, and 3) a small subset of T cells in the peripheral blood. Mouse monoclonal antibodies (two IgGs, one IgM, and F(ab')2 fragments) reacting with GD3 were found to stimulate proliferation of T cells derived from peripheral blood. Proliferation of T cells was observed even in cultures depleted of macrophages, suggesting that activation by anti-GD3 was not dependent on the presence of accessory cells. T cell proliferation was maximum between days 5 and 7 of stimulation and was preceded by expression of interleukin 2 receptors. No stimulation was observed with control antibodies of the identical isotype or with monoclonal antibodies recognizing the gangliosides GD2 or GM2. During stimulation by anti-GD3 monoclonal antibodies, there was an expansion of the GD3+ pool of T cells, but depletion of GD3+ T cells prior to stimulation abrogated the response. Proliferation induced by binding to GD3 could be augmented by exogenous interleukin 2 and phytohemagglutinin. Anti-CD3 (T3) monoclonal antibodies had little or no effect. These results demonstrate that binding to GD3 on the surface of T cells can elicit signals for T cell proliferation.
Characterization and antigen-presenting function of a murine thyroid-derived epithelial cell line.
Authors: Stein M E , Stadecker M J 
Published: December 2022

Abstract
We have developed and evaluated the antigen-presenting function of a murine thyroid-derived epithelial cell line M.5 in order to further investigate the possible role of the thyroid follicular epithelium in the inductive phase of autoimmune thyroiditis. M.5 cells did not express class II major histocompatibility complex encoded (Ia) antigens constitutively, but these could be readily induced with interferon-gamma. We found that Ia expressing M.5 cells were ineffective in stimulating T cell proliferation when tested in a 4-day primary mixed leukocyte reaction (MLR). However, significant T cell stimulation was obtained when phorbol myristate acetate (PMA) was added either to the M.5-T cell co-cultures, or for a brief period to the M.5 cells prior to adding the responder T cells. Cytofluorographic analysis of M.5 cells disclosed that PMA did not significantly alter the expression of Ia antigens. Additional experiments indicated that interleukin 1 (IL-1) was unlikely to represent the co-stimulatory factor generated by PMA. This was based on the observations that M.5 cells failed to secrete significant IL-1 either spontaneously, or in the presence of various stimuli, and that murine recombinant IL-1 failed to substitute for PMA in the activation of T cells. The nature of the co-stimulatory signal is as yet unknown. We conclude from these experiments that a pure population of thyroid-derived epithelial cells may be able to function, under the described circumstances, as antigen presenting cells.
Stimulation of endothelial cell binding of lymphocytes by tumor necrosis factor.
Authors: Cavender D , Saegusa Y , Ziff M 
Published: December 2022

Abstract
Lymphokines and monokines have been reported to affect endothelial cell (EC) morphology and function. In experiments here described, we have demonstrated that recombinant tumor necrosis factor (TNF) stimulates the adhesion of T lymphocytes to confluent monolayers of human umbilical vein EC. The increase in adhesion induced by TNF was EC-specific inasmuch as preincubation of the lymphocytes with TNF did not alter binding, and preincubation of human dermal fibroblasts with TNF did not increase their inherently low adhesiveness for lymphocytes. Stimulation of T-EC binding occurred after treatment of the EC with as little as 0.01 U/ml (1 pg/ml) of TNF. In kinetic experiments, preincubation of EC with TNF for 4 hr resulted in optimal adhesion. TNF-treated EC retained their increased adhesiveness after fixation with paraformaldehyde, suggesting that TNF stimulated binding by increasing the expression or accessibility of EC surface receptors for lymphocytes. Although antibodies to the lymphocyte function-associated antigen 1 alpha- or beta-chains on the T cell markedly inhibited unstimulated T-EC binding, such antibodies had no effect on the increase in EC adhesiveness induced by TNF, indicating that the increased binding resulted from the generation of an alternate binding receptor on the EC membrane. These findings provide additional evidence that cytokines participate in the mobilization of mononuclear cells in the chronic inflammatory reaction by stimulation of the adhesiveness of endothelium for circulating lymphocytes.
The in vivo effects of interleukin 1. I. Bone marrow cells are induced to cycle after administration of interleukin 1.
Authors: Neta R , Sztein M B , Oppenheim J J , Gillis S , Douches S D 
Published: December 2022

Abstract
We have previously reported that interleukin 1 (IL-1) administration 20 hr before irradiation protects mice from lethal effects of radiation. The recovery of total nucleated bone marrow cells and of hematopoietic progenitor cells was enhanced in IL-1 treated, as compared to untreated, irradiated mice. This suggested that IL-1 administration may affect the cells in the bone marrow of normal mice. Intraperitoneal administration of recombinant IL-1 resulted in bone marrow cell enlargement and increased cycling of these enlarged cells. In addition, the capacity of bone marrow cells from IL-1 treated mice to proliferate in response to granulocyte macrophage-colony-stimulating factor (GM-CSF) in cell suspension cultures was enhanced. The above effects were not genetically restricted as C57BL/6, B6D2F1, C3H/HeN, and C3H/HeJ mice showed similar responses. A comparative study showed that 100 ng of IL-1 was much more effective in stimulating bone marrow cells by the above criteria than 5 micrograms GM-CSF. Since IL-1, unlike CSF, can not be demonstrated to have a direct in vitro stimulatory effect on bone marrow cells, the aforementioned in vivo effects of IL-1 are presumably mediated by other hematopoietic growth factors. We have previously shown that IL-1 induces the appearance of high titers of CSF in the serum. Consequently hematopoietic growth factors that are generated at local sites following IL-1 administration may mediate the observed cell cycling effect.
Induction of interleukin 2 receptor (TAC) by tumor necrosis factor in YT cells.
Authors: Lee J C , Truneh A , Smith M F , Tsang K Y 
Published: December 2022

Abstract
The effect of human recombinant tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) on interleukin 2 receptor (IL-2R) expression on YT cells was examined. IL-2R expression was assessed by flow cytometric analysis with a monoclonal antibody to IL-2R (anti-TAC). TNF-alpha, like IL-1 beta, induced increased levels of IL-2R expression on YT cells with similar kinetics of induction. Maximum induction occurred at 20 to 30 hr. On a molar basis. TNF was less active than IL-1 beta. RNA isolated from TNF-alpha- or IL-1 beta-treated YT cells contained increased levels of IL-2R-specific mRNA as indicated by slot blot analysis by using an IL-2R-specific mRNA probe. Kinetic and IL-1 beta mRNA expression studies indicated that the TNF effect was a direct one. Because IL-2R expression is known to be associated with lymphocyte activation, the present results suggest that TNF-alpha may play a role in the regulation of immune responses.
Independent expression of a regulatory idiotype on heavy and light chains. A further immunochemical analysis with anti-heavy and anti-light chain antibodies.
Authors: Zanetti M , Rogers J 
Published: December 2022

Abstract
The heavy (H) and light (L) chains of murine monoclonal autoantibody 62 reacting with thyroglobulin independently express idiotypic (Id) determinants that are very similar if not identical with the Id62 expressed on the intact protein. In this report, we describe the production and characterization of rabbit antibodies to isolated H62 and L62 chains to further prove that individual chains express Id62 in an immunogenic form. The results demonstrate that both chains are capable of eliciting antibodies that, after appropriate adsorption, behave like conventional anti-Id62 antibodies prepared against the intact antibody molecule. By direct radioimmunoassay binding, competition of Id binding and Western blot anti-H62 and anti-L62 antibodies identify as Id-positive the same group of IgG1, bind in a reciprocal fashion to H- and L-chains of parental monoclonal antibody 62, and detect Id62-positive polyclonal serum autoantibodies to thyroglobulin. We conclude that monoclonal antibody 62 expresses independently a similar Id on both polypeptide chains and the intact antibody molecule, or its isolated chains, induce qualitatively similar anti-Id responses. These results are discussed in light of the possible structure/function implication such autoantibodies may have within the Id network.
Isotype concentrations of human antibodies to Haemophilus influenzae type b polysaccharide (Hib) in young adults immunized with the polysaccharide as such or conjugated to a protein (diphtheria toxoid).
Authors: Mäkelä O , Mattila P , Rautonen N , Seppälä I , Eskola J , Käyhty H 
Published: December 2022

Abstract
Antibody responses of young adults to Haemophilus influenzae type b polysaccharide (Hib) or its protein conjugate were studied with special attention to the isotype composition of the antibodies. Three conclusions of interest can be made: 1) Immunoglobulin G (IgG) antibodies in polysaccharide-immunized volunteers displayed the subclass pattern previously found in antibodies to meningococcal type A polysaccharide. IgG1 was the predominant subclass in IgG antibodies of some individuals, IgG2 in others. Still others had the two subclasses in varying but more even proportions. 2) The conjugate vaccine induced a geometric mean response 2 to 3 times higher and an IgG response 4 times higher to Hib than the polysaccharide vaccine. 3) Anti-Hib antibodies induced by the conjugate vaccine still had essentially the same IgG subclass composition as anti-Hib antibodies induced by the polysaccharide. This composition was strikingly different from the composition of the anti-diphtheria toxoid response induced by the same conjugate vaccine.
Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B.
Authors: Ferrari C , Penna A , Giuberti T , Tong M J , Ribera E , Fiaccadori F , Chisari F V 
Published: December 2022

Abstract
Hepatitis B core antigen (HBcAg)-specific T cell lines were established from hepatic lymphomononuclear cells derived from five patients with chronic active hepatitis B. No hepatitis B virus envelope antigen-specific cell lines were established. Proliferation in response to recombinant and native HBcAg, but not to native hepatitis B surface antigen containing the pre-S(2) region, confirmed the specificity of the five T cell lines. All cell lines represented mixed populations of CD4+ and CD8+ T cells. The CD4+ subset provided antigen-specific help to autologous B cells with respect to anti-HBc production and to CD8+ cells with regard to HBcAg-induced proliferation and suppressor activity. The CD8+ subset contained suppressor cells that selectively inhibited the proliferative response of autologous HBcAg-specific CD4+ cells without inhibiting CD4+ cells of unrelated specificity (tetanus toxoid). Moreover, the CD8+ cells were also capable of suppressing HBcAg-stimulated antibody to HBcAg production without showing inhibition of total immunoglobulin production stimulated by pokeweed mitogen. The cytotoxic potential of the T cell lines was established in a lectin-dependent cytotoxicity system; natural killer cytotoxicity was completely absent. Our data suggest that the lesional T cells present at the site of hepatocellular injury in chronic active hepatitis B are primarily HBcAg-specific lymphocytes of the helper and suppressor/cytotoxic phenotypes and that both are functionally competent.
Immunosuppressive activity of T cell clones generated from human T cells stimulated with autologous TPHA cells.
Authors: Gulwani B , Maio M , Imberti L , Melamede R J , Ferrone S 
Published: December 2022

Abstract
T cell clones were generated from human T cells stimulated with autologous phytohemagglutinin (PHA)-activated T (TPHA) cells. Characterization of three T cell clones originated from donor SF and one from donor JM showed that they proliferated when stimulated with autologous TPHA cells, non-T cells, and peripheral blood mononuclear cells, but did not proliferate when stimulated with allogeneic TPHA cells, non-T cells, and mononuclear cells, with autologous and allogeneic resting T cells, and with PHA. These results in conjunction with the blocking of the proliferation by anti-histocompatibility leukocyte antigen class II monoclonal antibodies indicate that these class II antigens are involved in the proliferation of T cell clones stimulated with autologous lymphoid cells. The four T cell clones are cytotoxic neither to autologous lymphoid cells nor to a panel of cultured human cell lines. The four T cell clones display immunosuppressive activity, since they inhibit the proliferation of autologous and allogeneic cells stimulated with antigens and mitogens and the secretion of immunoglobulin by B cells stimulated with pokeweed mitogen in presence of T cells. Furthermore, the four T cell clones display differential inhibitory activity on the proliferation of cultured human cell lines. The immunosuppressive activity is species-specific, since the T cell clones do not inhibit the proliferation of murine cells. The suppression is mediated by a factor(s) with an apparent m.w. of 13,000 to 16,000. The suppressor activity is labile at alkaline pH and is lost following incubation with pronase (100 U/ml) for 30 min at 37 degrees C.
Differential expression of nuclear proto-oncogenes in T cells triggered with mitogenic and nonmitogenic T3 and T11 activation signals.
Authors: Shipp M A , Reinherz E L 
Published: December 2022

Abstract
The relationship between induction of nuclear proto-oncogenes and cellular proliferation is not fully understood. To better define this relationship, we have studied c-fos, c-myc, and c-myb mRNA induction in T lymphocytes where early and late activation events have been clearly delineated. In T cells, initial activation from G0 to G1 results from stimulation of either the antigen/major histocompatibility complex receptor (T3-Ti) or the T11 structure; further cycle progression and proliferation follow interaction of interleukin 2 (IL-2) with the IL-2 receptor. These events can be dissected with monoclonal antibodies to T3 or T11 which cause early activation but differ in their ability to initiate IL-2-dependent cycle progression and proliferation. In T lymphocytes triggered through either T3-Ti or T11, c-fos is induced with a nonmitogenic activation signal whereas c-myb is only induced with a mitogenic signal capable of triggering IL-2 and IL-2 receptor expression. Furthermore, c-myc induction is biphasic and associated with both early and late activation events. Early c-myc, like c-fos, is induced with a nonmitogenic signal. In contrast, induction of late c-myc, like that of c-myb, requires a mitogenic signal. Thus, appearance of c-fos and initial c-myc mRNA seem to be early responses to membrane signaling whereas late c-myc and c-myb are more directly associated with actual cellular proliferation. That nonmitogenic stimulation of T cells via T3-Ti not only abrogates T11-mediated proliferation but also eliminates late c-myc and c-myb transcription further supports this notion.
Murine interstitial nephritis. VI. Characterization of the B cell response in anti-tubular basement membrane disease.
Authors: Clayman M D , Michaud L , Neilson E G 
Published: December 2022

Abstract
In the present study we have examined the murine B cell response in anti-tubular basement membrane (alpha TBM) disease. Whereas only certain strains of mice are susceptible to the development of interstitial lesions after immunization with heterologous renal tubular antigen, all strains make anti-tubular basement membrane antibodies (alpha TBM-Ab), and all express the 3M-1 kidney antigen which is the target of disease. The magnitude of the alpha TBM-Ab response in serum and renal eluates, measured by radioimmunoassay against crude tubular antigen or affinity-purified 3M-1, also mapped independently of susceptibility. The fine specificity of epitope binding was further analyzed using a rat monoclonal alpha 3M-1 antibody to competitively inhibit the binding of renal eluate antibody to 3M-1. Maximum inhibition among nearly all tested strains ranged from 46 to 56% with no discernible difference between susceptible and nonsusceptible mice. Idiotypic representation of renal eluate alpha TBM-Ab was then evaluated by competitive inhibition using a polymorphic anti-idiotypic antisera. All mice examined possessed almost identical competitive inhibition patterns, indicating surprisingly similar idiotypic representation. Thus, in susceptible or nonsusceptible mice, neither the quantitative alpha TBM-Ab response, the epitopic fine specificity of that response, nor the idiotype of eluted alpha TBM-Ab serve as distinguishing markers for susceptibility to interstitial injury. Finally, passive transfer experiments with high-titered (greater than 1:10,000) alpha TBM-Ab from SJL mice were performed to test the hypothesis that alpha TBM-Ab alone may be sufficient for the induction of alpha TBM disease. Whereas this antiserum was capable of causing typical, severe alpha TBM disease in naive susceptible SJL mice, this treatment in allotype-identical, nonsusceptible B10.S(8R) mice was completely without effect. These data demonstrate, in conclusion, that, in the absence of appropriate susceptibility genes, alpha TBM-Ab are incapable of causing alpha TBM disease. The findings support previous observations that the ability of passively transferred alpha TBM-Ab to initiate interstitial injury is dependent on the host also expressing other susceptibility genes which promote the cooperative engagement of the cell-mediated immune response.