Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antigenic Modulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1986

Regulation of human monocyte surface antigen expression. I. Up-modulation of Mo3e antigen expression on U-937 and HL-60 cells stimulated by pharmacologic activators of protein kinase C.

Mo3e is a protein (p 50,80) that is expressed on the surface of human monocytic cells after exposure in vitro to soluble activating factors that include bacterial lipopolysaccharide, muramyl dipeptide, and phorbol myristate acetate (PMA). The surface expression of Mo3e may represent a cellular event that occurs in response to the formation of "secondary messengers" that include diacylglycerol, inositol trisphosphate, and calcium ions. This postulate is based on the stimulatory effect of agents that can mimic the activity of endogenous diacylglycerol (PMA and other biologically active phorbol compounds, mezerein, and L-alpha-1,2 dioctanoylglycerol) and inositol trisphosphate (ionomycin) on Mo3e expression by U-937 and HL-60 cells. The inhibitory effect of phospholipid-active calmodulin inhibitors (trifluoperazine, chlorpromazine, and dibucaine), calcium antagonists (nicardipine and TMB-8), and EGTA further support the involvement of phospholipid- and calcium-dependent protein kinase (protein kinase C) and calcium ions in the up-modulation of Mo3e surface expression.

Antigens, Surface↗
PubMed1995

Interleukin 4 production by CD4+ T cells from allergic individuals is modulated by antigen concentration and antigen-presenting cell type.

We have previously shown that CD4+ T cells from allergic individuals are predisposed to produce interleukin (IL)-4 in response to allergens, and that allergen immunotherapy greatly reduced IL-4 production in an allergen-specific fashion. The mechanism that results in the reduction of IL-4 synthesis in treated individuals is unknown, but because clinical improvement during immunotherapy is associated with the administration of the highest doses of allergen, we hypothesized that high concentration of allergen results in the downregulation of IL-4 synthesis in CD4+ T cells. In this report, we demonstrated that CD4+ T cells from allergic donors produced high levels of IL-4 when stimulated with low concentrations of allergen (0.003-0.01 micrograms/ml), particularly when B cell-enriched populations presented the antigen. In contrast, the same responding CD4+ T cell population produced little IL-4 when stimulated with high concentrations of allergen (10-30 micrograms/ml), especially when monocytes were used as antigen-presenting cells (APC). The quantity of IL-4 produced was also found to be inversely related to the extent of proliferation of the CD4+ T cells in response to allergen/antigen; maximal proliferation of CD4+ T cells occurred in response to high concentrations of antigen when IL-4 production was minimal. Antigen presentation by B cell-enriched populations, instead of monocytes, induced less CD4+ T cell proliferation, but induced much greater IL-4 synthesis. Moreover, the addition of increasing numbers of APC (either B cells or monocytes) to cultures containing a constant number of responder T cells resulted in increased T cell proliferation and decreased IL-4 production. These results indicate that the circumstances under which memory T cells are activated, as well as the strength of the proliferative signal to T cells, greatly affect the quantity of IL-4 produced. Thus, our observations that the cytokine profile of allergen-specific memory CD4+ T cells can indeed be modulated by the antigen dose and APC type suggest that methods that preferentially enhance allergen uptake by monocytes and that enhance T cell proliferation will improve the clinical efficacy of immunotherapy in the treatment of allergic disease.

Allergens↗
PubMed2001

The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens and modulates the hepatitis delta virus RNA replication.

Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs). The small form of HDAg is required for HDV RNA replication, while the large form of HDAg inhibits the viral replication and is required for virion assembly. In this study, we found that the expression of B23, a nucleolar phosphoprotein involved in disparate functions including nuclear transport, cellular proliferation, and ribosome biogenesis, is up-regulated by these two HDAgs. Using in vivo and in vitro experimental approaches, we have demonstrated that both isoforms of HDAg can interact with B23 and their interaction domains were identified as the NH(2)-terminal fragment of each molecule encompassing the nuclear localization signal but not the coiled-coil region of HDAg. Sucrose gradient centrifugation analysis indicated that the majority of small HDAg, but a lesser amount of the large HDAg, co-sedimented with B23 and nucleolin in the large nuclear complex. Transient transfection experiments also indicated that introducing exogenous full-length B23, but not a mutated B23 defective in HDAg binding, enhanced HDV RNA replication. All together, our results reveal that HDAg has two distinct effects on nucleolar B23, up-regulation of its gene expression and the complex formation, which in turn regulates HDV RNA replication. Therefore, this work demonstrates the important role of nucleolar protein in regulating the HDV RNA replication through the complex formation with the key positive regulator being small HDAg.

Hepatitis Antigens↗
PubMed2006

Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by tumour-conditioned media retain the capacity to mature and induce TH1 T-cell proliferation.

The tumour microenvironment down-modulates antigen-presentation by dendritic cells (DC), presumably due to inhibition of DC maturation. Here, we sought to examine (1) whether monocyte-derived cells cultivated with tumour-conditioned media under conditions that are conducive to DC generation (APCTCM) resemble immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are functionally defective. Four tumour cell lines expressing different cytokines were used to mimic different tumour microenvironments. As compared to iDC, DCims or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and CD4. These markers and a high phagocytic capacity were unique features of these cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR and CD25 were up-regulated to levels considerably higher than in DCIL10 and comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated. Activated APCTCM induced 50-60% of the proliferative response of DCims in the allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC elicited approximately 10%). Activated APCTCM induced secretion of almost equal amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1 differentiation. When mature DCims were exposed to TCM, their immunostimulatory function was not significantly altered. However, when TCM were added to the co-cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the TCM. In summary, APCTCM display special features but can mature into DCims-like cells.

Antigen-Presenting Cells↗
PubMed1995

Tumour necrosis factors and several interleukins inhibit the growth and modulate the antigen expression of normal human melanocytes in vitro.

In the present study the action of various cytokines as regulators of human melanocyte growth and differentiation was examined in vitro. Primary melanocyte cultures were obtained in complete medium free of 12-O-tetradecanoylphorbol-13-acetate or serum. First passage melanocytes were treated with various concentrations of recombinant tumour necrosis factor alpha and beta (rTNF-alpha, rTNF-beta), as well as with various recombinant interleukins (rIL-1a, rIL-1b, rIL-2, rIL-3, rIL-4 and rIL-6) for 6 days in complete medium and for 6 and 12 days in a mitogen-reduced medium variant. The 4-methylumbelliferyl heptanoate fluorometric microassay and Ki-67 staining were used for assessing cell proliferation, and the immunophenotype was evaluated using various monoclonal antibodies. Melanocyte proliferation in complete medium was inhibited by rTNF-alpha (-24%), rTNF-beta (-17%), rIL-1a (-21%), rIL-1b (-18%) and rIL-6 (-29%); in contrast, rIL-2, rIL-3 and rIL-4 had no antiproliferative effect. Measurements of Ki-67-positive nuclei confirmed these results. In the reduced medium variant, none of the above cytokines inhibited melanocyte proliferation. Recombinant TNF-alpha and rTNF-beta markedly reduced the expression of the pigment cell-associated antigens HMB-45 and K.1.2, and they enhanced the expression of VLA-2, ICAM-1 and HLA class I antigens and strongly induced HLA-DR. Similar changes were induced by rIL-1a, rIL-b and rIL-6, and rIL-2 decreased the expression of HLA class I antigens and of ICAM-1. In conclusion, several cytokines inhibited the growth and modulated the phenotype of melanocytes in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed2005

Isolation and characterization of human anti-acetylcholine receptor monoclonal antibodies from transgenic mice expressing human immunoglobulin loci.

The isolation of human antibodies against muscle acetylcholine receptor (AChR), the autoantigen involved in myasthenia gravis (MG), is important for the development of therapeutically useful reagents. Monovalent antibody fragments from monoclonal antibodies against the main immunogenic region (MIR) of AChR protect the receptor from the destructive activity of MG autoantibodies. Human anti-AChR alpha-subunit antibody fragments with therapeutic potential have been isolated using phage display antibody libraries. An alternative approach for obtaining human mAb has been provided by the development of humanized mice. In this report, we show that immunization of transgenic mouse strains with the extracellular domain of the human AChR alpha-subunit results in antibody responses and isolation of hybridomas producing human mAb. Four specific IgM mAb were isolated and analyzed. mAb170 recognized the native receptor the best and was capable of inducing AChR antigenic modulation, suggesting its specificity for a pathogenic epitope. Moreover, the recombinant antigen-binding (Fab) fragment of this mAb competed with an anti-MIR mAb, revealing that its antigenic determinant lies in or near the MIR. Finally, Fab170 was able to compete with MG autoantibodies and protect the AChR against antigenic modulation induced by MG sera. This approach will be useful for isolating additional mAb with therapeutic potential against the other AChR subunits.

Amino Acid Sequence↗
PubMed2003

The strength of persistent antigenic stimulation modulates adaptive tolerance in peripheral CD4+ T cells.

The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.

Adaptation, Physiological↗
PubMed1983

Biological and clinical implications of lymphocyte hybridomas: tumor therapy with monoclonal antibodies.

Monoclonal antibodies of defined specificity can be produced using hybridoma technology. New attempts are being made to explore the potential of antibody therapy for cancer. Preliminary studies show that problems such as antigenic modulation, circulating free antigen, effector cell shortage, and host anti-mouse immunoglobulin response must be overcome. Uses of monoclonal antibodies in cancer treatment include the administration of unconjugated antibodies or of antibodies coupled to drugs, toxins, or radioisotopes, and the use of monoclonal antibodies in vitro to eradicate residual malignant cells.

Animals↗
PubMed1992

Effect of an anti-HLA class I monoclonal antibody on the antigenic and transcriptional expression of HLA class I genes in U937 cells.

The phenomenon of antigenic modulation was studied in the histiocytic lymphoma line U937. A redistribution of cell surface HLA antigen after incubation of U937 cells with the monomorphic anti-HLA class I monoclonal antibody W6/32 was demonstrated by immunofluorescence analysis. As assessed by hybridization of RNA obtained from W6/32-treated U937 cells with a probe corresponding to the alpha 3 domain of HLA Cw3, prolonged W6/32 incubation (24 to 72 hours) induced a decrease in HLA class I transcript abundance. This decrease was about 25% as compared with untreated control cells. These data indicate that W6/32 incubation can induce changes in HLA class I gene expression not only at the antigenic but also at the transcriptional level. Possible implications for the molecular basis of antigenic modulation are discussed.

Antibodies, Monoclonal↗
PubMed1997

Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation.

Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody (mAb) L243 significantly (P < 0.05) and differentially enhanced the release of tumor necrosis factor alpha (TNF-alpha) by the non-Hodgkin's lymphoma cells Ri-I, Ci-I, and Sc-I, which are at a distinct stage of B-cell differentiation, and by the more mature Burkitt lymphoma cell Raji; in contrast, it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173. TNF-alpha release peaked at 24 h and decreased thereafter, and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243. Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding activity; in fact, the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies did not upregulate NF-kappa B and AP-1. In contrast, released TNF-alpha was not responsible for the homotypic aggregation of Ri-I, Ci-I, Sc-I, and Raji cells induced by mAb L243, and it did not affect the proliferation of B cells investigated. Altogether, our data demonstrate that: (a) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation; (b) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens; (c) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop; and (d) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation.

Antibodies, Monoclonal↗
PubMed1977

Modulation of acetylcholine receptor by antibody against the receptor.

Antibody against acetylcholine receptor induces an increase in the rate of degradation of acetylcholine receptors on a mouse cell line (BC(3)H-1) and cultured rat skeletal muscle. The increased rate of degradation results in a lowered density of acetylcholine receptors on muscle membrane and a lowered sensitivity to iontophoretically applied acetylcholine. The modulation of acetylcholine receptor is energy, temperature, and time dependent and may be related to antigenic modulation found in other systems. Acetylcholine noise analysis demonstrates that antibody against acetylcholine receptor reduces the channel mean conductance and mean open time slightly. It is concluded that antibody binds to the acetylcholine receptor, impairs its function, and induces receptor degradation. This results in a lowered density of acetylcholine receptor and a lowered sensitivity to acetylcholine. Patients with myasthenia gravis have antibodies to their acetylcholine receptor in their serum. Antigenic modulation of receptor in the muscle of patients with myasthenia gravis could contribute to the observed decrease in amplitudes of miniature endplate potentials and in muscle acetylcholine sensitivity, and the symptoms of muscular weakness.

Acetylcholine↗
PubMed1984

The antigen of mature human B cells detected by the monoclonal antibody FMC7: studies on the nature of the antigen and modulation of its expression.

The monoclonal antibody FMC7 delineates a subpopulation of B lymphocytes in normal blood. Expression of the antigen recognized by FMC7 appears to be maturation-linked, and it serves to distinguish different types of B cell leukemia. The data presented here indicate that the antigen is a protein that is integrated in the cell membrane and that is able to interact with the cytoskeleton. The antigen is rapidly synthesized and turned over, is not cell cycle-dependent, and is relatively resistant to changes induced by culture in the presence of a phorbol ester.

Antibodies, Monoclonal↗
PubMed1995

Role of major histocompatibility complex class I antigens in modulating the performance of murine tumour cells in cold target competition assays.

The role of class I major histocompatibility complex (MHC) antigen levels on the ability of five murine tumour cell lines (YAC, P815, EL4, SP20 and L929) to competitively inhibit their own lysis, as well as the lysis of other targets by lymphokine-activated killer (LAK) effector cells was examined. Basal LAK susceptibilities of the cell lines were in the order P815 > YAC > SP20 > EL4 > L929, whereas the basal class I MHC antigen levels were in the order P815 > SP20 > L929 > YAC > EL4. Treatment with interferon-gamma (IFN-gamma) induced augmentation of class I MHC antigen levels on all cell lines. A concomitant decline in LAK susceptibility was seen for P815, YAC, SP20 and L929 cells, but not for EL4 target cells. On the basis of competition results, tumour cells appear to fall into two groups (group 1: P815, YAC and SP20; group 2: EL4 and L929). Members of each group could in general competitively inhibit the lysis of cell lines of their own group only. Treatment with IFN-gamma suppressed the ability of all tumour cell lines, except EL4, to cause competitive inhibition. These results support the proposition that class I MHC antigens may interfere with the recognition of target cells by effector LAK cells.

Animals↗
PubMed1993

Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human B-cell lines: an immunofluorescence and immunoelectron microscopy study.

Antibody-induced antigenic modulation (AIAM) of CD10 and CD19 was studied on NALM-6, RAJI, and JOK-1 cell lines using fluorescence microscopy (FM), flow cytometry (FCM), and immunoelectron microscopy (IEM). Cross-linking with monoclonal antibodies (MoAbs) induced rapid redistribution of CD10 and CD19 on the cell surface (FM) followed by internalization involving uptake through plasmalemmal pits, transfer through endosomal compartment (receptor-mediated endocytosis), and, finally, delivery to lysosomes for degradation or exocytosis and recycling (IEM). Significant quantitative differences regarding modulation and intracellular processing were shown by FCM and IEM. Thus, 35%, 30%, and 25% of CD10 compared with 80%, 60%, and 40% of CD19 were internalized in NALM-6, RAJI, and JOK-1 cells, respectively. Also, the rate of intracellular transfer as well as externalization and recycling was more pronounced in the case of CD19 than of CD10 and in the NALM-6 and RAJI cells compared with the JOK-1 cells. These differences may possibly reflect the functional significance of CD10 and CD19 as well as the stage of differentiation of the malignant B cells. Although both antigens can be useful in MoAb-targeted immunotherapy, our findings suggest that anti-CD19 MoAbs would be preferable for delivery of cytotoxic agents to malignant B cells.

Animals↗
PubMed1987

In vivo modulation of antigen presentation generates Ts rather than TDH in HSV-1 infection.

The role of suppressor cells in control of persistent infections may be of profound importance. Whether a positive immune response or suppression of immunity is generated at the time of initial exposure to pathogens causing such infections may in part be due to the nature of the initial antigen presentation to the specific cells of the immune system. We have shown that in vivo modulation of epidermal APCs by an environmentally encountered stimulus (UV-B light exposure) and subsequent transfer of these APCs together with live HSV-1 to naive syngeneic recipients is sufficient to generate suppression of DH rather than DH to HSV-1. This suppression is T-cell mediated and specific for HSV-1. The phenotype of the Ts cell induced by epidermal cell transfer is Thy1+ L3T4+ Ly2-.

Animals↗
PubMed1997

Cytokine modulation of antigen expression in human melanoma cell lines derived from primary and metastatic tumour tissues.

The constitutive and cytokine-mediated expression of MHC class I and II antigens and intercellular adhesion molecule-1 (ICAM-1) was evaluated on eight human melanoma cell lines derived from primary and metastatic malignancies from patients (WM human melanoma series) including three pairs of related cell lines derived from the same individual. The cytokines IL-1 beta, IL-4, IL-6, TNF alpha, TGF beta 2, IFN gamma and IFN alpha were assessed for their ability to modulate the expression of cell surface antigens. MHC class I and class II antigen expression was unregulated by IFN gamma, IFN alpha and/or TNF alpha in cell lines established from primary melanoma. In contrast the cell lines derived from metastatic deposits did not show an increase in expression of MHC antigens in response to these cytokines. Both primary and metastatic WM cell lines were shown to be resistant to spontaneous natural killer cell (NK) activity, but susceptible to effector lymphocytes mediating lymphotine activated killer (LAK) cytotoxicity as a result of activation by IL-2. Although the constitutive and cytokine-induced level of expression of ICAM-1 and MHC antigens varied between paired primary and metastatic cell lines, this did not correlate with susceptibility of the cell line target to NK or LAK cytotoxicity. Whereas the IFNs, TNF alpha, TGF beta 2 and IL-1 beta differentially modulated the expression of ICAM-1 and MHC class I, treatment with IFNs (but not IL-1 beta, TNF alpha or TGF beta 2) resulted in a significant reduction in the sensitivity of the melanoma cells to NK and LAK cytotoxicity. Constitutive ICAM-1 expression was positively correlated with the ability of WM cell lines to colonise the lungs of SCID mice upon i.v. injection. The acquisition of cytokine resistance and inability to demonstrate enhanced cell surface expression may represent an important feature associated with the development of the metastatic phenotype.

Animals↗
PubMed1994

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody.

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.

Antibodies, Monoclonal↗
PubMed2006

Modulation of antigenic phenotype in cultured human osteoblast-like cells by FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma.

BACKGROUND/AIMS: Recent reports demonstrated that osteoblast-like cells can also exert activities directly associated with the immune system (cytokine synthesis, antigen presentation, phagocytosis and stimulation of T lymphocytes). The present study aimed to analyze the effect of Transforming growth factorbeta1 (TGFbeta1), Fibroblast growth factor basic (FGFb), Platelet-derived growth factor-BB (PDGF-BB), Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Lipopolysaccharide (LPS) and Interferon-gamma (IFNgamma) on the expression on osteoblast-like cells of antigens involved in antigen presentation. METHODS: Flow cytometry was used to investigate whether the growth factors FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma modulate the expression on cultured human osteoblast-like cells of different antigens involved in antigen-presentation and T cell activation. RESULTS: TGFbeta1 treatment significantly reduced the expression of CD54 and CD86. IL-1beta treatment significantly enhanced the expression of CD54, CD86 and HLA-DR. LPS and IFNgamma treatments produced a major increase in CD54, CD80, CD86 and HLA-DR expression. Expression of these antigen-presenting molecules was not significantly modified by FGFb, PDGF-BB or IL-2 treatment.

Adult↗