bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative immunogenicity of hepatitis B virus core and E antigens.
Authors: Milich D R , McLachlan A , Stahl S , Wingfield P , Thornton G B , Hughes J L , Jones J E 
Published: December 2022

Abstract
The nucleocapsid (hepatitis B core Ag (HBcAg] of the hepatitis B virus is a particulate Ag composed of a single polypeptide (p21). Although a non-particulate form of HBcAg designated hepatitis B e Ag (HBeAg) shares significant amino acid identity, the immune responses to these Ag appear to be regulated independently. This report describes the use of recombinant HBcAg and HBeAg to examine and compare murine T cell and B cell recognition of these related Ag. The HBcAg preparation was stable at pH 7.2 and 9.6 and expressed HBc antigenicity. However, the antigenicity of the HBeAg preparation was pH dependent. At pH 9.6 the HBeAg preparation was non-particulate and expressed HBe antigenicity exclusively; however, at pH 7.2 it was particulate and expressed both HBc and HBe antigenicities. Although this "hybrid" particle most likely does not exist naturally, it is a unique research reagent to investigate the interrelationship between HBcAg and HBeAg. HBcAg was significantly more immunogenic in terms of in vivo antibody production as compared to either the non-particulate or particulate forms of HBeAg. Nevertheless, in most murine strains HBcAg and HBeAg were equivalently immunogenic and crossreactive at the level of T cell activation. The disparity between anti-HBc and anti-HBe antibody production is best explained by the observation that HBcAg can function as a T cell-independent Ag whereas HBeAg is T cell dependent even when present within the same particulate structure as HBcAg. Furthermore, HBcAg was shown to function efficiently as an immunologic carrier moiety for the DNP hapten in athymic as well as euthymic mice in contrast to conventional carrier proteins. These results have implications relevant to the human immune responses to HBcAg and HBeAg during infection, and to vaccine development.
Inhibition of CD4+ T cell function by the HIV envelope protein, gp120.
Authors: Diamond D C , Sleckman B P , Gregory T , Lasky L A , Greenstein J L , Burakoff S J 
Published: December 2022

Abstract
The CD4 molecule is functionally involved in the class II MHC-restricted T cell response to Ag. CD4 is also the receptor for HIV-1, the major etiologic agent of AIDS. We have assessed whether the interaction of the HIV-1 envelope protein with the CD4 molecule might interfere with the normal function of CD4, thereby contributing to the immunosuppression observed after HIV infection. Using a murine T cell hybridoma which expresses the human CD4 protein and exhibits a CD4-dependent response to Ag, we demonstrate that the HIV envelope protein gp120 can specifically inhibit this response.
Induction of anti-CD8 resistant cytotoxic T lymphocytes by anti-CD8 antibodies. Functional evidence for T cell signaling induced by multi-valent cross-linking of CD8 on precursor cells.
Authors: McCarthy S A , Kaldjian E , Singer A 
Published: December 2022

Abstract
The effector function of most MHC class I allospecific CTL is inhibited by anti-CD8 mAb. In the present study, we report the surprising observation that multi-valent cross-linking of CD8 molecules on precursor cells by specific antibody actively induces the generation of CD8+ class I allospecific CTL whose lytic function is resistant to anti-CD8 antibody inhibition, and actively induces down-modulation of cell surface CD8 expression on these cells. In marked contrast, bi-valent cross-linking of CD8 inhibits the generation of CD8+ CTL from precursor cells and fails to induce down-modulation of cell surface CD8 expression. These results demonstrate that CD8 can transduce net positive signals, but only when the molecule is extensively cross-linked.
The generation of alloreactive cytotoxic T lymphocytes requires the expression of ecto-5'nucleotidase activity.
Authors: Massaia M , Pileri A , Boccadoro M , Bianchi A , Palumbo A , Dianzani U 
Published: December 2022

Abstract
Ecto-5'-nucleotidase (ecto-5'NT) activity is highly expressed by CTL precursor cells. The aim of this work was to investigate whether ecto-5'NT is involved in their functional activation. The inhibition of ecto-5'NT activity by biochemical (alpha,beta-methyleneadenosine 5-diphosphate; AOPCP) or immunologic inhibitors (polyclonal anti-ecto-5'NT serum) suppressed the proliferative and cytotoxic activation of CTL against a lymphoblastic B cell line in primary one-way MLC. The kinetic analysis of suppression showed that AOPCP and anti-5'NT serum had different effects: AOPCP suppressed only the activation of the cytotoxic program whereas anti-5'NT serum suppressed also recognition and binding to the stimulatory/target cell. Inhibition of CTL generation was not a metabolic consequence of the purine salvage blockade. Incubation of AOPCP-treated MLC with hypoxanthine restored proliferation but not cytotoxicity. The ecto-5'NT inhibitors used had no general toxic effect on cell numbers or viability. AOPCP selectively affected CTL generation and displayed no activity against mitogen-induced proliferation, activation of Ts cells, and generation of IL-2-activated killer cells. These data indicate that ecto-5'NT has a critical role in the functional activation of alloreactive CTL.
Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane.
Authors: Paccaud J P , Carpentier J L , Schifferli J A 
Published: December 2022

Abstract
C receptors 1 (CR1) of human E are involved in the transport of C3b-coated immune complexes (IC) in the circulation. Many studies have suggested that the binding of IC to E is multivalent. This would require CR1 to be clustered on the cell membrane, but no direct evidence for such clustering is available. We studied the distribution of CR1 on human E by immunofluorescence and shadow-casting immuno-electron microscopy techniques with the use of a monoclonal anti-CR1 antibody followed by FITC- or gold-conjugated second antibodies, respectively. By immunofluorescence, CR1 appeared as small dots (clusters) on fixed and unfixed E prepared either at 4 degrees C or at 37 degrees C. In the same donor, the number of clusters varied extensively from cell to cell (e.g., 1 to 43 clusters/E for a donor with 520 CR1/cell), but the mean number of clusters per cell correlated significantly with the mean number of CR1/cell. These images contrasted with those obtained for Rhesus D (RhD) Ag used as controls (RhD Ag are known to be evenly distributed): only a faint uniform fluorescence was seen despite the presence of 10,000 antigenic sites. As determined by immunocytochemical method, more than 65% of the total gold particles were organized in clusters (2 to 15 gold particles/cluster) whether cells were prefixed or not. Quantitative determinations suggested that each gold particle corresponded to one CR1. The fraction of gold particles grouped into clusters of three or more receptors, the mean size of the clusters, and the maximal size of clusters correlated with the mean number of CR1 per cell. By contrast, RhD Ag were distributed homogeneously (less than 2% gold particles in clusters). These data are the first to demonstrate the preclustered nature of CR1 on E. Such distribution could explain the high binding efficiency of C3b-coated IC to E despite the low number of CR1 per cell.
Biochemical characterization of membrane cofactor protein of the complement system.
Authors: Ballard L L , Bora N S , Yu G H , Atkinson J P 
Published: December 2022

Abstract
Membrane cofactor protein (MCP; formerly termed glycoprotein 45-70 to indicate its Mr) of complement is a widely distributed iC3/C3b binding protein with co-factor activity. On human mononuclear cells and cell lines and platelets, MCP is a doublet. The two forms differ in Mr by approximately 5 k and the upper species is predominant in most individuals. To further characterize these two forms, limited proteolytic digestions were performed. Of the four peptides produced, three have identical Mr indicating that the molecules are similar proteins. Both forms also have acidic isoelectric points and shift to a less acidic isoelectric point after treatment with neuraminidase. Glycosidase digestions indicate that both species contain N- and O-linked oligosaccharides but that the quantity of sialic acid is greater on the larger one. Pulse-chase experiments demonstrate approximately equal quantities of two precursor forms with Mr of 41 and 43 k. These two precursors possess N-linked high-mannose type of oligosaccharides and chase into the mature molecules which have complex sugars. The smaller precursor chases at a slower rate, possibly accounting for the reduced quantity of the smaller form of the mature form of MCP. These experiments indicate that the two forms of MCP are structurally similar and are derived from two distinct precursors. They also suggest that variations in the rate of processing of two intracellular precursors may account for the different quantities of the mature forms of this membrane protein.
Lack of detectable somatic hypermutation in the V region of the Ig H chain gene of a human chronic B lymphocytic leukemia.
Authors: Meeker T C , Grimaldi J C , O'Rourke R , Loeb J , Juliusson G , Einhorn S 
Published: December 2022

Abstract
Monoclonal human B cell tumors are a model system for the study of somatic hypermutation of the Ig genes of humans. It was previously shown that a number of B cell lymphomas exhibited striking V region point mutation, hypothesized to result from the somatic hypermutation mechanism. In this study we have extended the analysis to chronic lymphocytic leukemia. We have cloned and sequenced the productive Vh representing five different cells from a monoclonal chronic lymphocytic leukemia. All five Vh sequences were identical. Therefore, the Vh region in this leukemia was not the subject of detectable somatic mutation. These data suggest that chronic lymphocytic leukemia might lack the mechanism for somatic hypermutation and represent a stage of normal B lymphocyte differentiation in which the somatic hypermutation mechanism is not active.
Protection of cultured human monocytes from lymphokine-activated killer-mediated lysis by IFN-gamma.
Authors: Blanchard D K , Djeu J Y 
Published: December 2022

Abstract
We have recently reported that IL 2-activated killer (LAK) cells are capable of lysing cultured human monocytes. In an effort to protect autologous monocytes from lysis, we treated monolayer cultures of adherent PBMC with various doses of human rIFN-gamma and assessed their susceptibility to LAK cells. IFN-gamma was shown to lessen the sensitivity of monocytes to lysis in a dose-dependent manner. Similar treatment of FMEX, an NK-resistant melanoma tumor cell line, with IFN-gamma did not affect its susceptibility to LAK lysis. Kinetic studies demonstrated that as little as 2 h incubation with IFN-gamma was sufficient for the protective effects to take effect. Additionally, monocytes that were pulsed with IFN-gamma for 2 h, washed, and then cultured in medium alone retained their resistance to lysis for at least 3 days. Cold target inhibition studies showed that IFN-treated and untreated monocytes could effectively compete with each other for binding sites on LAK cells. Furthermore, binding studies demonstrated that there was no significant difference between the number of conjugates formed by using either IFN-treated or untreated monocytes. This indicates that resistance to lysis induced by IFN treatment affects a post-binding event and not an initial recognition signal. From these studies, it was apparent that treatment of monocytes with IFN-gamma lessened their sensitivity to LAK-mediated lysis. Thus, it may be possible through a specific sequence of IFN-gamma and IL-2 treatment that LAK activity could be manipulated against some tumor cells, but not normal cells, to abrogate some of the toxicity seen with this type of cancer therapy.
The C4 and C2 but not C1 components of complement are responsible for the complement activation triggered by the Ra-reactive factor.
Authors: Ji Y H , Matsushita M , Okada H , Fujita T , Kawakami M 
Published: December 2022

Abstract
Ra-reactive factors (RaRF) are the name of a group of C-dependent bactericidal factors that bind specifically to Ra chemotype strains of Salmonella. These factors are present in the sera of a wide variety of vertebrates and have common characteristics. Here we investigate the C components required for the C activation induced by mouse RaRF, by using hemolysis of Ra LPS-coated E (ELPS) as a model system. It was found that C1-depleted and C1q-depleted sera were as effective as the undepleted serum in the lysis of ELPS sensitized with RaRF. Addition of the C1 component or C1q subcomponent to the depleted sera did not increase the effect. On the other hand, C4 and C2 components were found to be essential for the lysis of RaRF-sensitized ELPS. Activities of C4 and C2 remained on the sensitized cells even after washing the cells, suggesting that the classical C3 convertase, C4b2a, is generated on the RaRF-sensitized ELPS.
A monoclonal antibody that inhibits secretion from rat basophilic leukemia cells and binds to a novel membrane component.
Authors: Ortega Soto E , Pecht I 
Published: December 2022

Abstract
Rat basophilic leukemia (RBL-2H3) cells, like mast cells and basophils, carry monovalent membrane receptors with high affinity for IgE (Fc epsilon R). Cross-linking of these receptors provides the immunologic stimulus which initiates a series of biochemical events, culminating in secretion of inflammatory mediators. In an attempt to identify membrane components involved in the stimulus-secretion coupling of these cells, hybridomas were produced from splenocytes of mice immunized with intact RBL-2H3 cells. Here we report the production of a mAb (designated G63) that inhibits the Fc epsilon R-mediated secretion from RBL cells. At low degrees of Fc epsilon R aggregation, the mAb G63-induced inhibition may be complete, whereas at the maximum of secretion the inhibition is in the range of 30 to 40%. The relative degree of inhibition of secretion is dependent on the dose of mAb G63. Furthermore, inhibition requires the bivalency of G63, as the Fab fragments are inactive. The number of antigenic epitopes recognized by G63 per RBL-2H3 cell is 1.8 x 10(4) epitopes/cell, as determined by direct binding studies of 125I-labeled Fab fragments of G63. This number is 20 to 30 times smaller than that of Fc epsilon R on the same cells. The membrane component to which G63 binds has been identified by immunoprecipitation as a glycoprotein with an apparent Mr of 58 to 70 kDa. All of these results, and the fact that no competition for binding to RBL cells between mAb G63 and IgE can be resolved, indicate that mAb G63 binds to a membrane component which is distinct from the Fc epsilon R. mAb G63 suppresses the Fc epsilon R-mediated rise in cytoplasmic concentration of free Ca2+ ions, known to be one of the biochemical signals involved in the stimulus-secretion coupling in RBL-2H3 cells. G63 does not affect, however, the degranulation induced by the Ca2+ ionophore A23187. Therefore, mAb G63 probably exerts its inhibitory effect on a step preceding the rise in cytoplasmic free Ca2+. Thus, mAb G63 defines a previously unidentified membrane component that is involved in one of the early steps of the RBL-2H3 activation mediated by their Fc epsilon R.
Suppression of lymphokine-activated killer induction by neutrophils.
Authors: Shau H Y , Kim A 
Published: December 2022

Abstract
Peripheral blood polymorphonuclear neutrophils (PMN) suppressed the induction of PBL lymphokine-activated killer (LAK) function by rIL-2 in vitro. The suppression depended on the concentration of PMN in the IL-2 culture, and required intact PMN. However, PMN did not require treatment with immunoregulators such as IL-2, LPS, or TNF to express the suppressive activity, and no direct contact with PBL was needed for the suppression. Addition of anti-TNF antibodies had no effect on the suppression, suggesting that no endogenous TNF in the culture was involved in the suppression. PMN did not inhibit LAK function by preventing utilization of IL-2 by PBL or by selective depletion of NKH-1+ cells which constitute the majority of LAK precursors in PBL. The suppression was reversed by superoxide dismutase but not by catalase, suggesting that superoxide anion, not hydrogen peroxide, was involved in the suppression. No other suppressive factor was detectable in PMN culture supernates. Our results of PMN regulating LAK induction in vitro suggest that PMN may have a role in determining the outcome of immunotherapy with IL-2 in vivo.
Differential recognition by human cytotoxic T cell clones of human M1 fibroblasts transfected with an HLA-B7 gene (JY150) suggests the existence of two different HLA-B7 alleles in the cell line JY (HLA-A2,2;B7,7;Cw-,-;DR4,w6).
Authors: van Seventer G A , Spits H , Yssel H , Melief C J , Ivanyi P 
Published: December 2022

Abstract
We have used a panel of human HLA-B7-specific CTL clones to identify an HLA-B7 gene (JY150) transfected into human M1 fibroblasts (M1/B7). Only a subset of the CTL clones recognized the M1/B7 cells, whereas all CTL clones recognized the donor of the B7 gene, the cell line JY (HLA-A2,2;B7,7;Cw-,-;DR4,w6). Analysis of the fine specificity of these CTL clones was performed by testing the reactivity on M1 cells transfected with an HLA-B27K gene and on a panel of cell lines typed for HLA-B7 subtypes (variants). These results, combined with one-dimensional IEF analysis of the M1/B7 cells and the B7 subtypes, indicated that the differential recognition by the CTL clones of the transfected gene was not caused by aberrant expression of the gene itself or due to the absence of critical accessory molecules on the M1 fibroblast cells. Our data suggest that the widely used HLA-B7 reference cell line JY is not homozygous at the HLA-B locus, but contains two different B7 alleles encoding the B7.2 and B7.4 subtypes.
Allogeneic T cell activation triggering by MHC class I antigens.
Authors: Chouaib S , Bensussan A , Termijtelen A M , Andreeff M , Marchiol-Fournigault C , Fradelizi D , Dupont B 
Published: December 2022

Abstract
The role of MHC-encoded class I molecules in allogeneic activation and proliferation of human T lymphocytes was investigated. The study was performed by using primary mixed culture of lymphocytes from MHC recombinant siblings identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. The results indicate that such allogeneic combination is sufficient to trigger early activation steps within responder T cells without promoting a significant proliferation. After MHC class I allosensitization, a significant proportion of cells entered the cell cycle (G0----G1). The stimulatory potential of MHC class I Ag was further stressed by the specific induction on responder cells of IL-2R (22% T cell activation Ag positive). Under the same experimental conditions, transferrin receptor expression and IL-2 activity were not detectable. This is consistent with the low T cell proliferation. Exogenous rIL-1 did not improve IL-2 production and the subsequent T cell proliferation indicating that these two events were not associated with a defective accessory cell function involving IL-1 release. MHC class I disparity can also prime precursor CTL to differentiate into IL-2-dependent functional MHC restricted cytotoxic T cells. Conversely IFN-gamma had no effect. Addition to the culture of W6/32, a mAb specifically directed against a monomorphic determinant on human class I HLA-A, -B, and -C Ag was able to block all these activation events. These data clearly indicate a role of HLA class I Ag involvement in the early events triggering allogeneic T cell activation.
IL-4 induces co-expression of intrinsic membrane IgG1 and IgE by murine B cells stimulated with lipopolysaccharide.
Authors: Snapper C M , Finkelman F D , Stefany D , Conrad D H , Paul W E 
Published: December 2022

Abstract
IL-4 promotes IgG1 and IgE secretion by murine B cells stimulated with bacterial LPS. We show that stimulation of unprimed resting splenic B cells with LPS and 10(4) U/ml rIL-4 results in the expression of membrane (m) IgG1 and mIgE on 40 to 50% and 15 to 25% of the total B cell population, respectively, on day 4 of culture. The possibility of a significant contribution to cell surface staining by cytophilic, secreted Ig isotypes was eliminated by either the addition of anti-Fc gamma or anti-Fc epsilon R mAb during the culture or by acid treatment before staining. A similar proportion of IgE-expressing B cells are also found, after stimulation with LPS and 10(4) U/ml IL-4, by cytoplasmic staining using fluorescence microscopy. Cell sorting analysis further indicates that B cell populations that express mIgG1 and mIgE secrete these respective Ig isotypes. In addition, such cells show striking diminution in IgM secretion compared to mIgG1- or mIgE- sorted B cells. Stimulation with LPS and IL-4 (10(4) U/ml) induces co-expression of mIgG1 and mIgE on LPS-stimulated B cells; up to 75% of mIgE+ B cells co-express mIgG1 and up to 19% of mIgG1+ B cells express mIgE. This striking co-expression of mIgG1 and mIgE is mirrored by the co-expression of mIgG1 with mIgG3 and mIgG2b by B cells stimulated with LPS and 200 U/ml IL-4. Cell sorting analysis demonstrates that the B cell population that co-expresses mIgG1 and mIgE secretes both IgG1 and IgE. However, "two-color" cytoplasmic staining fails to demonstrate any B cells that simultaneously secrete both IgG1 and IgE.
Stimulation of human neutrophil adhesive properties by adenine nucleotides.
Authors: Freyer D R , Boxer L A , Axtell R A , Todd R F 
Published: December 2022

Abstract
Inasmuch as adenine nucleotides may be secreted by platelets during inflammation, we sought to determine whether ATP and related compounds could serve as stimuli of neutrophil (polymorphonuclear cells, PMN) activation as manifested by an increase in their adhesive properties. Exposure of isolated human PMN to ATP or its nonhydrolyzable analog, adenosine 5'-O-(3-thiotriphosphate) did indeed stimulate an increase in cellular adhesive function as assessed by an increase in the surface expression of the leukocyte adhesion-promoting glycoprotein, Mo1 (CD11b/CD18), the initiation of PMN aggregation, and (in the case of ATP) the attachment of increased numbers of albumin-coated polystyrene latex beads. However, this increase in PMN adhesive function was not accompanied by the generation of products of the respiratory burst. These in vitro data suggest the possible influence of secreted adenine nucleotides in promoting neutrophil adhesion-dependent interactions at inflammatory sites in vivo.