bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 2 receptors are expressed by alveolar macrophages during pulmonary sarcoidosis and are inducible by lymphokine treatment of normal human lung macrophages, blood monocytes, and monocyte cell lines.
Authors: Hancock W W , Muller W A , Cotran R S 
Published: December 2022

Abstract
Expression of receptors for IL 2 was believed initially to be restricted to T cells after their activation by IL 1 and antigen. However, recently IL 2 receptors (IL 2R) were demonstrated on activated B cells by using an anti-IL 2R monoclonal antibody (anti-Tac). In this study, we examined the capacity of cultured human alveolar macrophages, blood monocytes, and myelomonocytic (HL-60) or monoblast (U937) cell lines to bind three different anti-IL 2R monoclonal antibodies before or after stimulation with the monocyte-activating agents IFN-gamma, LPS, phorbol ester, or lymphokine-containing conditioned medium. For each of the four cell populations examined, resting unstimulated cells bound little or no anti-IL 2R antibody, as shown independently by quantitative cell binding assay and by immunoperoxidase labeling. By contrast, incubation with recombinant IFN-gamma, conditioned medium, or to a lesser extent, native or recombinant IL 2 itself, resulted in a significant enhancement of anti-IL 2 receptor monoclonal antibody binding by all four populations, whereas LPS, PMA, or IL 1 had no effect. In addition, membrane binding of anti-Tac antibody, similar to that seen after stimulation of normal lung macrophages with IFN-gamma, was detected by using macrophages obtained by bronchoalveolar lavage of five patients with active pulmonary sarcoidosis. These findings are consistent with the expression of a functional IL 2R on activated cells of the monocyte lineage, since anti-Tac binding to IFN-gamma-treated HL-60 cells was inhibited by addition of excess IL-2; specific binding of anti-IL 2 monoclonal antibodies was detected in the presence of exogenous IL 2; and a 50 to 55 kD molecule was immunoprecipitated from both activated lung macrophages and T lymphoblasts by using anti-Tac antibody. We conclude that human mononuclear phagocytes can be induced by lymphokines to express IL 2R, and that such IL 2R+ macrophages can be detected in vivo during inflammation.
Spontaneous production of a suppressor factor by a human macrophage-like cell line U937. II. Suppression of antigen- and mitogen-induced blastogenesis, IL 2 production and IL 2 receptor expression in T lymphocytes.
Authors: Fujiwara H , Toossi Z , Ohnishi K , Edmonds K , Ellner J J 
Published: December 2022

Abstract
U937, a human macrophage-like cell line, spontaneously produces a factor which inhibited blastogenic responses of human blood T lymphocytes stimulated with tuberculin-purified protein derivative (PPD) or phytohemagglutinin (PHA). We investigated the mechanism of suppressor action of the U937 factor. The U937 suppressor factor inhibited interleukin 2 (IL 2) production by human blood T lymphocytes stimulated with PPD or PHA. IL 1 did not overcome the inhibitory action of the U937 factor on PPD-induced IL 2 production by human blood T lymphocytes. The U937 factor also inhibited the production of IL 2 by a human leukemic cell line, JURKAT, stimulated with PHA. The U937 suppressor factor interfered with the expression of Tac antigen (IL 2 receptor) on PPD- or PHA-stimulated blood T lymphocytes. The inhibitory activity of the U937 factor on Tac expression was not affected by the addition of IL 2 or a crude lymphokine-containing T cell supernatant. Tac expression was more sensitive than IL 2 production to inhibition by U937-conditioned medium. The U937 suppressor factor was precipitable by 33 to 67% saturated ammonium sulfate and was inactivated at pH 2 or pH 11. Sephacryl S-200 Gel filtration analysis of U937 culture supernatants revealed that the inhibitory activities for blastogenesis, IL 2 production, and Tac expression co-purified in fractions with an apparent m.w. between 67,000 and 130,000. These data indicate that U937 spontaneously produces a macromolecular suppressive factor with major locus of action on the production of IL 2 and the expression of the IL 2 receptor.
Strong conformational propensities enhance T cell antigenicity.
Authors: Spouge J L , Guy H R , Cornette J L , Margalit H , Cease K , Berzofsky J A , DeLisi C 
Published: December 2022

Abstract
The ability to predict T cell antigenic peptides would have important implications for the development of artificial vaccines. As a first step towards prediction, this report uses a new statistical technique to discover and evaluate peptide properties correlating with T cell antigenicity. This technique employs Monte Carlo computer experiments and is applicable to many problems involving protein or DNA. The technique is used to evaluate the contribution of various peptide properties to helper T cell antigenicity. The properties investigated include amphipathicities (alpha and beta), conformational propensities (alpha, beta, turn and coil), and the correlates of alpha-helices, such as the absence of helix-breakers and the positioning of the residues which stabilize alpha-helical dipoles. We also investigate segmental amphipathicity. (A peptide has this property when it contains at least two disjoint subpeptides, one hydrophobic, one hydrophilic.) Statistical correlations and stratifications assessed independent contributions to T cell antigenicity. The findings presented here have important implications for the manufacture of peptide vaccines. These implications are as follows: if possible, peptide vaccines should probably be those protein segments which have a propensity to form amphipathic alpha-helices, which do not have regions with a propensity to coil conformations, and which have a lysine at their COOH-terminus. The last two observations are of particular use in manufacturing peptides vaccines: they indicate where the synthetic peptides should be terminated. These implications are supported by the findings given below. The significances (p values) support the following statistical generalites about antigenic conformations: most helper T cell antigenic sites are amphipathic alpha-helices; alpha-helical amphipathicity and propensity to an alpha-helical conformation contribute independently to T cell antigenicity; there is evidence that some T cell antigenic sites are beta conformations instead of alpha-helices; T cell antigenic sites avoid random coiled conformations; and T cell antigenic sites are usually not segmentally amphipathic. alpha-Helical amphipathicity was significant, but segmental amphipathicity was not. This has implications for the dimensions of the structure interacting with the hydrophobic portion of an amphipathic T cell antigenic site. Lysines are unusually frequent at the COOH-terminal of T cell antigenic sites, even after accounting for tryptic digests. These lysines can stabilize alpha-helical peptides by a favorable interaction with alpha-helical dipoles.(ABSTRACT TRUNCATED AT 400 WORDS)
Interaction of IgG3 anti-streptococcal group A carbohydrate (GAC) antibody with streptococcal group A vaccine: enhancing and inhibiting effects of anti-GAC, anti-isotypic, and anti-idiotypic antibodies.
Authors: Greenspan N S , Monafo W J , Davie J M 
Published: December 2022

Abstract
Enhancement of binding of one monoclonal antibody to an antigen in the presence of a second monoclonal antibody (specific for an independent epitope on the same antigen) has been observed for several antigen-antibody systems involving primarily protein, or glycoprotein, antigens. We have analyzed the interaction between radiolabeled IgG3 kappa anti-streptococcal group A carbohydrate (GAC) antibody (125I-HGAC 39) and streptococcal group A vaccine (GAV; traditionally used to elicit anti-GAC antibody) in the absence and presence of unlabeled anti-GAC antibodies, anti-isotypic antibodies, or anti-idiotypic antibodies, respectively. A variety of significant enhancing or inhibiting effects on the binding of 125I-HGAC 39 to solid-phase GAV (GAVsp) were noted. First, high concentrations of IgG3 anti-GAC antibodies specifically inhibit binding of 125I-HGAC 39 to GAVsp, but the presence of lower concentrations of IgG3 anti-GAC antibodies is associated with markedly increased (up to 300 to 400%) binding of 125I-HGAC 39 to GAVsp. In contrast, with the concentrations used, IgM anti-GAC antibodies only inhibit binding of 125I-HGAC 39 to GAVsp. A monoclonal anti-gamma 3 antibody (2E.6) also enhances binding (up to 700%) of 125I-HGAC 39 to GAVsp, whereas another high-affinity anti-isotypic antibody, anti-C kappa (187.1), only inhibits binding of 125I-HGAC 39 to GAVsp. In a similar manner, an antiidiotypic antibody (anti-IdX) specific for a framework idiotope located near the C kappa domain inhibits the interaction between 125I-HGAC 39 and GAVsp. Evidence is presented to suggest that neither anti-C kappa nor anti-IdX blocks the HGAC 39 paratope, and therefore, the inhibition of binding mediated by these antibodies must be on some other basis. An alternative explanation for this effect, on the basis of the impairment of functional bivalency of 125I-HGAC 39, is discussed. Finally, anti-idiotypic antibodies (anti-IdI-3a and anti-IdI-1) that bind closer to the antigen-binding site of HGAC 39 inhibit binding of 125I-HGAC 39 to GAVsp in a manner that is most readily interpreted as competition for the GAC-binding site (or nearby sites) on the HGAC 39 variable domain. These effects are shown to require specific immunologic recognition of either GAVsp or 125I-HGAC 39.
Infectivity of Leishmania braziliensis promastigotes is dependent on the increasing expression of a 65,000-dalton surface antigen.
Authors: Kweider M , Lemesre J L , Darcy F , Kusnierz J P , Capron A , Santoro F 
Published: December 2022

Abstract
Sequential development of Leishmania braziliensis promastigotes from a noninfective to an infective stage was demonstrated. The generation of infective forms was related to their growth cycle and restricted to stationary stage organisms. Using immunofluorescence techniques, we have noticed that the binding of a monoclonal antibody (mAb) against L. braziliensis (VD5/25) increased progressively as the promastigotes developed in culture and was maximal with the infective forms. This antigenic differentiation was not detected with an anti-L. braziliensis polyclonal rabbit antiserum, suggesting that only a few epitopes, including that recognized by VD5/25, have their expression effectively increased on the surface of infective promastigotes. Immunoprecipitation of lysates of surface-iodinated L. braziliensis promastigotes with this mAb revealed two proteins of apparent 65,000 and 50,000 Mr, the 50,000 Mr protein probably representing the unreduced form of the major surface glycoprotein described in several species of Leishmania (GP65). The increasing expression of this epitope was not found with L. chagasi promastigotes, but seems to occur with the parasites from the L. mexicana complex. Intracellular survival of L. braziliensis was completely inhibited when the infective promastigotes were treated with VD5/25. It appears, therefore, that the increasing expression of GP65 on the promastigote surface represents an essential mechanism of leishmania survival in the macrophage.
Novel V genes encode virtually identical variable regions of six murine monoclonal anti-bromelain-treated red blood cell autoantibodies.
Authors: Reininger L , Ollier P , Poncet P , Kaushik A , Jaton J C 
Published: December 2022

Abstract
The variable (V) region sequences of six immunoglobulin M (IgM, kappa) monoclonal autoantibodies that recognize bromelinized isologous red blood cells, obtained by fusions of peritoneal cells from NZB or CBA/J nonimmunized mice with BALB/c myeloma cells, were determined by direct mRNA sequencing. The V regions of the light chains (VL) are almost identical with one another, as are the V regions of the heavy chains (VH), which, however, differ by six linked-base substitutions, depending on the strain of mice producing the autoantibodies. Such variations may reflect allelic differences. The VH segments determined have no obvious correspondence to any VH genes identified so far. They may belong to the small VH group 4, where 73% homology, at the most, can be calculated at the protein level for codons 1 to 94. Alternatively, the VH regions may be members of a new group of VH sequences not previously found. The V kappa regions appear closely homologous to members of the V kappa-9 subgroup of myeloma proteins of unknown antigen-binding specificity. The joining segments, J kappa and JH, used by the autoantibodies investigated, originate from the J kappa 2 and JH1 germ-line gene segments, respectively. The nine base-long diversity segments, D, derive from one member of the germ-line D gene SP2 family.
Spontaneous in vitro evolution of lytic specificity of cytotoxic T lymphocyte clones isolated from murine intestinal epithelium.
Authors: Klein J R , Kagnoff M F 
Published: December 2022

Abstract
Three long-term clonally derived cytotoxic lines have been established from isolates of murine intraepithelial lymphocytes (IEL). All three lines were selected for with antigen and represent two allospecific cytotoxic T lymphocyte (CTL) clones and a major histocompatibility complex (MHC)-restricted clone specific for a murine minor histocompatibility antigen. On long-term in vitro culture, IEL clones gradually lost antigen-specific lytic activity and simultaneously acquired the capacity to lyse natural killer (NK)-sensitive target cells which, in some cases, required high-level lymphokine activation. Of interest was the finding that, despite changes in lytic specificity, IEL clones remained strictly antigen-dependent for proliferation. A murine CTL clone of splenic origin, which was propagated under culture conditions identical to those used for IEL, did not exhibit changes in lytic specificity, suggesting that acquired changes in IEL function cannot be attributed solely to the influence of in vitro culture. Phenotypic analyses of IEL clones with altered lytic specificity revealed that all lines remained Thy-1+, Lyt-2+, L3T4-, with or without lytic activation by lymphokines. The expression of CT-1, a murine CTL activation antigen, and asialo GM1, a murine NK cell marker, were variable on IEL clones, and their presence did not correlate with the changes in lytic behavior. Collectively, these findings provide evidence, at the clonal level, that at least some NK activity present in isolates of murine IEL may originate from antigen-specific CTL. The data also indicate that, on binding antigen, different signals are conveyed to T cells, resulting in proliferation or target cell lysis.
Heterogeneity of signal requirements in T cell activation within a panel of human proliferative T cell clones.
Authors: Goronzy J , Weyand C , Imboden J , Manger B , Fathman C G 
Published: December 2022

Abstract
Activation of T lymphocytes is initiated by receptor ligand interactions at the cell surface leading to the transduction of intracellular signals followed by the de novo synthesis and expression of T cell activation markers (including receptors for interleukin 2 (IL 2) and transferrin), production of lymphokines, and T cell proliferation. This requisite first step for activation of T lymphocytes can be mimicked in certain situations with a variety of stimuli. These include antibodies to certain integral membrane proteins, phorbol esters, and plant lectins that act as mitogens. In this paper, we report that at least two classes of human T cell clones can be distinguished based upon signal requirements necessary to induce proliferation. Although all clones analyzed expressed IL 2 receptors and secreted IL 2 after non-antigenic activation, one subset of clones did not proliferate in response to the same non-antigenic signals. In that subset, complete activation leading to proliferation required interaction of the T cell with specific antigen. The ability to subset these T cell clones into two groups did not correlate with phenotypic differences, source of the clone, nor with magnitude of intracellular calcium mobilization. By studying the stimulation requirements of these two subsets of human T cell clones through the use of specific antigen or antigen-independent stimuli, it was possible to demonstrate that different stimuli varied in their ability to induce steps of T cell activation. Analysis of reactivity of these clones to suboptimal stimulation allowed the definition of intermediate stages of T cell activation. Such intermediate stages might reflect a diversity of intracellular signaling pathways or a complexity of regulatory mechanisms distal to the events that allow intracellular calcium mobilization. Thus for the first time, it has been possible to study ordered events of T cell activation in non-transformed, antigen-dependent human T lymphocytes. The data presented in this paper suggest that T cell activation is not an all or nothing phenomenon, and there is an ordered sequence of events that can be differentiated based upon signal requirements at the T cell membrane.
Activation of immature cortical thymocytes through the T11 sheep erythrocyte binding protein.
Authors: Blue M L , Daley J F , Levine H , Craig K A , Schlossman S F 
Published: December 2022

Abstract
Two major pathways, the T cell receptor and the T11 alternate pathway, allow for T cell activation. In the human thymus, the T cell antigen receptor complex is reduced or absent on immature thymocytes, whereas the T11 glycoprotein is present at high cell surface density on all thymocytes. To determine whether activation through the T11 pathway induces similar or different changes in mature and immature thymocytes, we fractionated thymocytes according to their surface expression of the T3-T cell receptor (T3/Ti) complex. We report that two populations, one with high and one with low T3/Ti expression, can be activated through the T11 pathway to undergo nuclear activation and express IL 2 receptors. Moreover, in the absence of accessory cells, only the most mature population, expressing high T3 density, could be induced to proliferate, whereas the subset representing immature cortical thymocytes required accessory cells for proliferation. These findings suggest that the cellular microenvironment may have a critical role in regulating the activation of immature cortical thymocytes and that this cell population may not represent "nonfunctional" dead end cells, but rather a valid intermediate in human thymic differentiation.
Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells.
Authors: Keizer G D , Borst J , Visser W , Schwarting R , de Vries J E , Figdor C G 
Published: December 2022

Abstract
The p150,95 heterodimer, one of three members of the leukocyte function associated antigen (LFA) family, is expressed by monocytes, granulocytes, NK cells, and a small percentage of lymphocytes. We now report that the p150,95 glycoprotein is expressed by some cytotoxic T cell clones and that it is involved in cell-mediated cytolysis by these clones. Two CTL clones, clone JS-93 (CD3+ CD4+ CD8-) and clone JS-102 (CD3+ CD4- CD8+) expressed high levels of p150,95 and were shown to be specifically directed against HLA-DR and HLA-A2, respectively. Immunoprecipitations followed by two-dimensional gel electrophoresis demonstrated no heterogeneity in the p150,95 molecule isolated from both clones. Furthermore, we demonstrated that monoclonal antibodies (moab) directed against p150,95 could inhibit the cytotoxic activity of both clone JS-93 and clone JS-102 (50% and 47%, respectively). Single cell assays revealed the inhibition to occur at the level of conjugate formation rather than at the level of the lethal hit. Similar results were obtained with moab directed against LFA-1 (p170,95). The capacity of the moab directed against LFA-1 and p150,95 to inhibit CTL activity and conjugate formation were additive, resulting in a similar percentage of inhibition as found with moab directed against the common beta-chain of these molecules. It is concluded that at least some CTL clones express the p150,95 antigen at their cell surface, and that this molecule, like LFA-1, acts at the level of conjugate formation between effector and target cells.
Regulation of cytolytic activity in CD3- and CD3+ killer cell clones by monoclonal antibodies (anti-CD16, anti-CD2, anti-CD3) depends on subclass specificity of target cell IgG-FcR.
Authors: van de Griend R J , Bolhuis R L , Stoter G , Roozemond R C 
Published: December 2022

Abstract
Anti-CD3 MAb can inhibit MHC-restricted cytolytic activity of CD3+ mature cytotoxic T cells. In particular effector-target cell combinations, however, anti-CD3 MAb enhance or induce cytolysis by cross-linking CD3+ effector and IgG-FcR+ target cells. Virtually all natural killer (NK) cells or NK cell-derived clones are CD3-4-8- but do express CD2 and CD16 (IgG-FcR) antigens. We have studied how these cell surface molecules are involved in the regulation of cytolytic activities. The addition of anti-CD2 MAb to effector and target cells was found to induce conjugate formation of the IgG-FcR+ target cells with the effector cell and nonspecific cytolysis of, for instance, the P815 mouse mastocytoma cells. Enhancement or induction of conjugate formation and cytolysis of IgG-FcR+, P815, U937, and Daudi cells was also accomplished by using anti-CD16 MAb (e.g., Leu-11c (B73.1) or CLB Fc-gran 1 (VD2) MAb). Some human and mouse tumor cell lines (K562, P815, and U937) appear to express distinct types of IgG-FcR, showing different affinities for distinct subclasses of MAb (e.g., IgG1, IgG2a), but another line (Daudi) expresses only one type of IgG-FcR preferentially binding IgG1 MAb. Here we demonstrate that IgG-FcR on the effector cells can act as activation sites because anti-CD3 as well as anti-CD16 MAb of IgG1 and IgG2a subclasses can induce lytic activity of target cells bearing the relevant IgG-FcR. These data demonstrate that induction of conjugate formation and cytolysis by MAb occur when the target cells bear IgG-FcR with "specificity" for those MAb. Thus, besides via CD3, cytolytic activity by mature T and NK cells also can be induced via the CD2 and CD16 antigens on these cells.