Antigen modulation of the immune response. V. Generation of large memory cells in antigen draining lymph nodes.
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Animals↗
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Results for “Antigenic Modulation”
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Immunologic injury in measles virus infection. II. Suppression of immune injury through antigenic modulation.
Upon the addition of antibody to measles virus, measles virus antigens expressed on the surface of infected cells can be modulated from the cell's membrane in vitro. Removal of measles virus antigens from the surface of cells occurs relatively rapidly and is accompanied by a parallel reduction in the ability of antibody and complement to lyse these cells. Modulation of surface viral antigens can occur in the absence of cap formation and is fully reversible once measles virus antibodies are removed from culture medium. Protracted exposure of acutely infected cells to measles virus antibodies results in a population of cells that exhibit normal cytomorphology and growth behavior. These cells continue to express measles virus antigens internally, but not at the cell surface, and are refractory to immune lysis. Once antiviral antibody is removed, measles virus antigens again appear on the cell surface, giant cell and syncytial formation occur, and cell death follows. These observations may explain the persistence of virus in spite of a vigorous host antiviral immune response in certain chronic infections of man.
Antibodies, Viral↗
In vitro antigenic modulation of human neuroblastoma cells induced by IFN-gamma, retinoic acid and dibutyryl cyclic AMP.
Testing with a panel of 26 monoclonal antibodies (MAbs) showed the antigenic profile of 13 human neuroblastoma cell lines to be characterized by a generally poor antigenic expression; therefore, Interferon-gamma (IFN-gamma), dibutyryl cyclic-AMP and retinoic acid were used to analyse the modulation of surface antigenic expression during differentiation. Treatment of neuroblastoma cell lines with IFN-gamma resulted mainly in induction or increase of class-I MHC antigenic expression. Induction of class-II MHC antigens was obtained on only one neuroblastoma cell line out of 13, thus representing an exceptional event. An increase in some other antigens expressed by neuroblastoma cell lines was also observed. In contrast, and in addition to morphological maturation, treatment of these cell lines with the differentiation inducer dibutyryl-cyclic-AMP (dbc-AMP), resulted in general down-modulation of antigenic expression, particularly of neuroblastoma-associated 5A7 or Leu7 antigens. Retinoic acid treatment had no significant effect on MHC antigens, but it decreased expression of 5A7 and Leu7 antigens, and markedly increased the expression of the melanoma-associated antigen Me14-D12. The similarity between the antigenic profile of in vitro differentiated neuroblastoma cells and that of mature ganglioneuroma cells suggests that compounds like cyclic-AMP or retinoic acid are excellent tools for further investigations of the mechanisms of neuroblastoma differentiation and might have important clinical applications.
Antigens, Neoplasm↗
Three-dimensional patterns of antigenic modulation of Haemophilus pertussis, H. parapertussis and H. bronchisepticus.
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Antigenic Modulation↗
Antigenic modulation in retinoblastoma: a flow cytometric study.
Flow cytometry (FCM) was used to investigate antigenic expression and modulation during the cell cycle of Y-79 and WERI-Rb1 tissue cultured retinoblastoma cell lines using a polyclonal anti-Y-79 antibody and fluorescein conjugated lectins. Several Y-79 resting cell populations were identified by FCM analysis of antibody binding, while only a single population with uniform antigen expression was found to exist in the synthetic and mitotic phases. WERI-Rb1 cells bound antibody approximately equally in each phase of the cell cycle. Multiple cell populations with different lectin binding affinities were seen in the resting phase with FITC-concanavalin A, FITC-ricinus communis-60 and FITC-ricinus communis-120 (FITC-RCA-120). During the S-phase of the cell cycle, a higher percentage of cells bound FITC-RCA-120 and FITC wheat germ agglutinin. The relationship between antigenic expression during the cell cycle and treatment considerations in retinoblastoma is discussed.
Antibodies, Anti-Idiotypic↗
Simian virus 40 large tumor antigen modulates the Raf signaling pathway.
The large tumor antigen of simian virus 40 (SVLT) is a potent oncogene. Although inactivation of the p53 and pRb tumor suppressors has been causally linked to the transforming properties of SVLT, its exact mechanism of action remains undefined. Previous data indicated that Ras is activated in SVLT-expressing cells. In this report we show that SVLT also increases Raf kinase activity in both insect and mammalian cells, thus identifying the Raf kinase as an additional target of SVLT. Our results further show that SVLT was still able to activate Raf in cells where Ras levels had been drastically reduced through expression of an antisense construct, indicating that SVLT may activate Raf at least partly by a mechanism that is independent of its stimulatory effect on Ras.
Animals↗
Antigen modulation of the immune response. The decline of immunological memory in the absence of continuing antigenic stimulation.
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Ammonium Sulfate↗
Editorial: Antigenic modulation.
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Animals↗
Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C1-Barcelona.
Foot-and-mouth disease virus (FMDV) isolate C(1)-Barcelona (or C-S30) includes four replacements within its immunodominant site (GH loop, residues 136-150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C-S8c1 (YTASARGDLAHLTTT). Although one of the mutations in C-S30 (147Leu-->Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised against FMDV C1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8c1 or C1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation that 15-residue peptides reproducing the C-S30 and C-S8c1 GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Nevertheless, surface plasmon resonance (SPR) kinetic analyses of the interactions between these peptides and three anti-GH loop mAbs have now revealed that the linear C-S30 peptides were less antigenic in solution than their C-S8c1 and C1-Brescia counterparts. We have, therefore, tried to modulate peptide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-1H NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation seems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved.
Amino Acid Sequence↗
Rapidity of antigenic modulation of Bordetella pertussis in modified Hornibrook medium.
Modulation of Bordetella pertussis was induced by growth in Hornibrook medium with a high content of magnesium sulphate (C-medium); four pathophysiological activities in the cells or in the whole culture were measured at intervals. Modulation, shown by the extensive loss of protective antigen, histamine-sensitising factor, leuko-cytosis-promoting factor, heat-labile toxin and X-mode specific envelope proteins, occurred during the first 10 h of incubation of X-mode cells in C-medium at 35 degrees C and before the onset of the logarithmic phase of growth. The rapidity of these losses was greater than could be explained by a simple growth-dilution effect and did not appear to be due to release of activity into the culture fluid. It seemed, therefore, that there was selective destruction of pathophysiological activities as well as cessation of synthesis. The activities appeared to be lost at different rates. Mouse-protective activity was lost more rapidly than histamine-sensitising and leukocytosis-promoting activities; heat-labile toxicity was lost more slowly or less completely. Modulation was shown to be easily reversed.
Adjuvants, Immunologic↗
Interaction of JC virus agno protein with T antigen modulates transcription and replication of the viral genome in glial cells.
In addition to encoding the structural and regulatory proteins, many viruses encode auxiliary proteins, some of which have been shown to play important roles in lytic and latent states of the viruses. The human neurotropic JC virus (JCV) genome encodes an auxiliary protein called Agno whose function remains unknown. Here, we investigated the functional role of JCV Agno protein on transcription and replication of the viral genome in glial cells. Results from transfection of human glial cells showed that Agno protein suppresses both T-antigen-mediated transcription of the viral late gene promoter and T-antigen-induced replication of viral DNA. Affinity chromatography and coimmunoprecipitation assays demonstrated that the Agno protein and T antigen physically interact with each other. Through the use of a series of deletion mutants, we demonstrated that the T-antigen-interacting region of Agno protein is localized to its amino-terminal half and the Agno-interacting domain of T antigen maps to its central portion. Furthermore, utilizing various Agno deletion mutants in functional studies, we confirmed the importance of the Agno-T antigen interaction in the observed down-modulation of T antigen function upon viral gene transcription and DNA replication by Agno protein. Taken together these data suggest that the Agno protein of JCV, which is produced late during the late phase of the lytic cycle, can physically and functionally interact with the viral early protein, T antigen, and downregulate viral gene expression and DNA replication. The importance of these observations in the lytic cycle of JCV is discussed.
Amino Acid Sequence↗
The cytoplasmic tail of invariant chain modulates antigen processing and presentation.
The MHC class II-associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of Iip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and Ii itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distribution in the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an Ii-dependent MHC class II-restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest that this causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the Iip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation.
Amino Acid Substitution↗
Interaction of mAb to angiotensin-converting enzyme (ACE) with antigen in vitro and in vivo: antibody targeting to the lung induces ACE antigenic modulation.
We previously described that mAb to angiotensin-converting enzyme (ACE), mAb 9B9, accumulates in the rat lungs after systemic injection. In the present work we have documented that mAb 9B9 cross-reacts with human, monkey, rat, cat and hamster ACE, while other ACE antibodies did not cross-react with the rat, cat and hamster enzyme. Anti-ACE mAb 3A5 and I2H5 inhibit human ACE in vitro, while mAb 9B9 does not inhibit ACE activity. Radiolabeled mAb 9B9, but not other antibodies, accumulates selectively in rat, cat and hamster lungs after systemic administration. No accumulation of mAb 9B9 has been observed in hamster kidney, while hamster kidney ACE activity is higher than that in the lung. mAb 9B9 does not induce complement-mediated injury to cultured endothelial cells. No pathological changes were detected in organs of animals after mAb 9B9 injection (10-100 mg/kg). However, injection of these amounts of mAb 9B9 leads to a decrease in ACE activity in the lung homogenates and an increase in serum. In cultured human endothelial cells treatment with mAb 9B9 increases ACE activity in cell medium and decreases in cell lysates. Therefore, while mAb 9B9 does not kill endothelial cells, at high dose it may induce ACE shedding from the cell. The results obtained support the potential of anti-ACE mAb 9B9 for targeting to the lung and for investigations of the pulmonary endothelium.
Animals↗
Differential susceptibility to recombinant interferon-gamma-induced HLA-DQ antigen modulation among clones from a human metastatic melanoma.
Twenty-one clones from an early culture of a histocompatibility leukocyte antigen (HLA) class II negative human metastatic melanoma (Me 9229) were screened for susceptibility to phenotypic modulation induced by recombinant interferon-gamma (rIFN-gamma) by using SPV-L3, a monoclonal antibody to HLA-DQ antigens, in indirect immunofluorescence followed by fluorescence-activated cell sorter analysis. After treatment with 500 U/ml of rIFN-gamma for 3 days one of the clones (9229/18) expressed high levels of DQ antigens, in terms of percentage of positive cells, whereas many other clones were much less susceptible or remained DQ negative. Scatchard analysis of the data of specific binding of 125-I-labeled rIFN-gamma revealed that one clone susceptible (9229/18) and one clone resistant (9229/5) to HLA-DQ modulation expressed similar numbers of interferon-gamma binding sites per cell; dose-response experiments showed that all clones could be induced to express HLA-DR and -DP antigens after exposure to rIFN-gamma. However, the DQ-negative profile of clone 9229/5 was not modified even after incubation with up to 1 X 10(4) U/ml of rIFN-gamma or by extending the culture time in the presence of this lymphokine up to 120 hr. Furthermore, Northern blot analysis indicated a direct correlation between changes in the levels of HLA-DR and -DQ-specific mRNA after rIFN-gamma treatment, and the lack or expression of HLA class II antigens at the cell surface of the two different clones. Karyotype studies did not reveal differences between clones 9229/5 and 9229/18 and Southern blot analysis indicated that both clones had similar EcoRI and HindIII restriction patterns for DR and DQ gene sequences. Finally, strong DQ-specific mRNA signal and antigen expression at the cell surface could be induced even on clone 9229/5 by treating the cells with supernatants from mixed lymphocyte cultures, recently shown to contain a class II-inducing factor different from interferon-gamma. Taken together these results indicate that DQ antigens can be modulated even in clones resistant to rIFN-gamma induction and suggest that the differential susceptibility observed in response to this lymphokine could play a role in the genesis of the phenomenon of intratumor heterogeneity.
DNA, Neoplasm↗
Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells.
The activation of an abnormal glycosylation pathway in cancer cells leads to the formation of the sialyl-Tn antigen, blocking regular carbohydrate chain elongation. Sialyl-Tn antigen is rarely expressed in normal tissues but is aberrantly expressed in a variety of carcinomas, where it constitutes a marker of poor prognosis. Although the clinical significance of sialyl-Tn is well characterized, a functional role for this glycan and its contribution to cancer progression remain to be elucidated. This study evaluates the capability of sialyl-Tn to modify processes like cell cycle, apoptosis, actin cytoskeleton dynamics, adhesion and motility on ECM components, cell-cell aggregation and invasion. De-novo expression of sialyl-Tn leads to major morphological and cell behavior alterations in gastric carcinoma cells which were reverted by specific antibody blockage. Sialyl-Tn antigen is able to modulate a malignant phenotype inducing a more aggressive cell behavior, such as decreased cell-cell aggregation and increased ECM adhesion, migration and invasion.
Antigens, Neoplasm↗
Polyomavirus middle-sized tumor antigen modulates c-Jun phosphorylation and transcriptional activity.
Polyomavirus middle-sized tumor antigen (MT) increases the expression of c-jun through a phorbol 12-O-tetradecanoate 13-acetate response element in the c-jun promoter. To investigate the cellular signaling pathways affected by MT, we studied the role of the c-Ras and Raf-1 proteins in MT-induced transactivation of c-jun and cell transformation. There was an increase in GTP complexed to Ras in MT-expressing cells, indicating an increase in Ras activity. Coexpression of dominant inhibitory mutants of Ha-ras and raf-1 with MT inhibited MT-mediated transactivation and focus formation. Studies of the phosphorylation of c-Jun showed that MT expression increased the phosphorylation of Ser-63 and Ser-73 in the transactivation domain and decreased the phosphorylation of a peptide containing Ser-243, Ser-249, and Thr-231 in the DNA binding domain. MT increased the transcriptional activating ability of c-Jun but failed to increase the transcriptional activating ability of c-Jun mutants with Ser-63 and Ser-73 changed to nonphosphorylatable Ala, indicating that MT modulates c-Jun activity through phosphorylation. The dominant inhibitory mutants of Ha-ras and raf-1 interfered with the ability of MT to activate c-Jun. The results indicate that MT induces a phosphorylation cascade through the activation of c-Ras and Raf-1 and that c-Jun is one of the downstream targets that may cause changes in gene expression leading to cell transformation.
3T3 Cells↗
Prostate-specific antigen modulates the expression of genes involved in prostate tumor growth.
Prostate-specific antigen (PSA) is a serine protease that is widely used as a surrogate marker in the early diagnosis and management of prostate cancer. The physiological relevance of tissue PSA levels and their role in prostate tumor growth and metastasis are not known. Free-PSA (f-PSA) was purified to homogeneity from human seminal plasma by column chromatography, eliminating hk2 and all known PSA complexes and retaining its protease activity. Confluent monolayers of prostate cancer cell lines, PC-3M and LNCaP, were treated with f-PSA in a series of in vitro experiments to determine the changes in expression of various genes that are known to regulate tumor growth and metastasis. Gene array, quantitative polymerase chain reaction (QPCR), and enzyme-linked immunosorbent assay (ELISA) results show significant changes in the expression of various cancer-related genes in PC-3M and LNCaP cells treated with f-PSA. In a gene array analysis of PC-3M cells treated with 10 muM f-PSA, 136 genes were upregulated and 137 genes were downregulated. In LNCaP cells treated with an identical concentration of f-PSA, a total of 793 genes was regulated. QPCR analysis reveals that the genes for urokinase-type plasminogen activator (uPA), VEGF, and Pim-1 oncogene, known to promote tumor growth, were significantly downregulated, whereas IFN-gamma, known to be a tumor-suppressor gene, was significantly upregulated in f-PSA-treated PC-3M cells. The effect of f-PSA on VEGF and IFN-gamma gene expression and on protein release in PC-3M cells was distinctly dose-dependent. In vivo studies showed a significant reduction (P = .03) in tumor load when f-PSA was administered in the tumor vicinity of PC-3M tumor-bearing BALB/c nude mice. Our data support the hypothesis that f-PSA plays a significant role in prostate tumor growth by regulating various proangiogenic and antiangiogenic growth factors.
Animals↗
Quantitative analysis of CD5 antigen modulation by 12-O-tetradecanoylphorbol-13-acetate in T-lymphoblastic leukemia cells: individual response patterns and their relationships with both maturation and protein kinase C content.
Modulation of CD5 expression by TPA was investigated on T-leukemic cell lines corresponding to different stages of ontogeny. These CD5 changes have been analyzed simultaneously with modifications of cell growth, cell cycle, cell surface phenotype, and PKC content. CD5 expression was found 6- to 17-fold increased by TPA in a dose-dependent manner on phenotypically mature T-cells (Jurkat, JM, and T-CLL) while T-cells from earlier stages of differentiation (CEM III, CEM 95, and CEM 44) were found unresponsive. CD5 upregulation on TPA-sensitive JM cells appears correlated with inhibition of cell growth, blockage in G1 phase, and phenotypic maturation (downregulation of CD7 and CD1 antigens) and seemed to be related to PKC activation since DiC8 (a PKC activator) mimicked this TPA effect and H7 (a PKC inhibitor) partially reduced it. On the other hand, on CEM III cells TPA induced no modulation of CD5 antigen, a less dramatic effect on cell growth and cell cycle, but a CD7 downregulation. TPA appeared fully effective in binding and translocating PKC in both CEM III and JM cells, although the PKC activity level was three times higher in the latter. Finally, our study suggests that CD5 expression is at least partially under control of PKC in phenotypically mature neoplastic T-cells while PKC could not be directly involved in the regulation of CD5 antigen in leukemic cells arrested at earlier stages of differentiation.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗