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.

SourceResearch connectionFrom yearThrough year

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

At least 415 records · Page 23Linked to original sources

PubMed1996

SV40 T antigen increases the expression and activities of p34cdc2, cyclin A, and cyclin B prior to immortalization of human diploid fibroblasts.

SV40 T antigen induces karyotype instability soon after it is expressed in human diploid fibroblasts and ultimately promotes cell immortalization and tumorigenesis. Protein levels and activities of mitotic cell cycle proteins have been shown to be elevated in several immortal cell lines relative to their normal parental cells, suggesting a possible role for the aberrant regulation of mitosis in karyotype instability. We show here that IMR-90 human diploid lung fibroblasts expressing the SV40 tumor antigens display increased protein levels and associated enzymatic activities of cyclin A, cyclin B, and p34cdc2 long before crisis and immortalization. These elevations cannot be explained by faster cell growth or altered cell cycle distributions. Increased protein levels were not totally accounted for by elevated levels of the corresponding mRNA, indicating that T antigen modulates expression at least partially by posttranscriptional mechanisms. These results indicate that perturbation of mitotic regulatory proteins precedes crisis, and imply that altered mitotic control is a direct consequence of T antigen expression rather than an outcome of secondary events associated with immortalization.

Amino Acid Sequence↗

PubMed1998

Antigenic variation and the murine immune response to Giardia lamblia.

The protozoan parasite Giardia lamblia is an important causative agent of acute or chronic diarrhoea in humans and various animals. During infection, the parasite survives the host's reactions by undergoing continuous antigenic variation of its major surface antigen, named VSP (variant surface protein). The VSPs form a unique family of cysteine-rich proteins that are extremely heterogeneous in size. The relevance of antigenic variation for the survival in the host has been most successfully studied by performing experimental infections in a combined mother/offspring mouse system and by using the G. lamblia clone GS/M-83-H7 (human isolate) as model parasite. In-vivo antigenic variation of G. lamblia clone GS/M-83-H7 is characterised by a diversification of the intestinal parasite population into a complex mixture of different variant antigen types. It could be shown that maternally transferred lactogenic anti-VSP IgA antibodies exhibit cytotoxic activity on the Giardia variant-specific trophozoites in suckling mice, and thus express a modulatory function on the proliferative parasite population characteristics. Complementarily, in-vitro as well as in-vivo experiments in adult animals indicated that non-immunological factors such as intestinal proteases may interfere into the process of antigen variation in that they favour proliferation of those variant antigen-type populations which resist the hostile physiological conditions within the intestine. These observations suggest that an interplay between immunological and physiological factors, rather than one of these two factor alone, modulates antigenic diversification of a G. lamblia population within an experimental murine host and thus influences the survival rate and strategy of the parasite.

Animals↗

PubMed1985

[Design and synthesis of conjugates between antineoplastic agents and monoclonal antibodies].

The production of conjugates between anti-tumor agents and monoclonal antibodies in order to achieve a more selective therapy of cancer has been a research field in continuous expansion during the last years. The present study is directed towards trying to define a practice guide to be used in the design and synthesis of this type of conjugates. The points considered refer to the characteristics which have to be taken into account of each of the parts which constitute the conjugate (monoclonal antibody or fragments and the anti-tumor agent) and also of the method of synthesis, according to our experience and experience gained in other laboratories. The qualities studied of the antibody are its specificity towards tumour cells, intrinsic cytotoxicity, molecular size, antigenicity, resistance to manipulation, biological half life and antigenic modulation properties. Referent to the cytotoxic agent the properties to deal with are its toxicity, presence of functional groups, hydrophobicity, ionic charge, unspecific interaction sites, molecular weight, resistance to manipulation and antigenicity. The characteristics to take into account of the method of synthesis are its simplicity, the homogeneity of the products obtained, the difficulty in purifying the products, the smoothness of the reaction and the type of conjugate formed (that is, whether the agent has been directly linked to the antibody or linked to it via a "bridge" molecule). The ideal characteristics referring to every one of these points have been selected having in mind the possibility of clinical application of this type of conjugates that we expect to have a specific cytotoxic action on tumour cells once the antibody has been selectively localized in the tumour and has targeted there the cytotoxic agent coupled to it. Some of the points studied are, however, still open to further evaluation.

Antibodies, Monoclonal↗

PubMed1985

Monoclonal antibody to human cytotoxic-suppressor T-lymphocytes cross-reacts with canine lymphocytes and inhibits cell-mediated lympholysis of canine cells.

Of 19 murine antihuman Tp32 (T8) monoclonal antibodies tested, only antibody T811 showed cross-reactivity with canine lymphoid cells. It recognized an antigen expressed on 19%-27% of peripheral blood mononuclear cells (PBMC), 20%-30% of peripheral Thy 1+ T-lymphocytes, 40% of puppy thymocytes, 35%-45% of alloantigen-activated peripheral lymphocytes, and 100% of PBMC from a dog with acute T-cell leukemia. The antigen was not expressed on peripheral Thy 1- cells, bronchoalveolar cells, or null-type acute leukemia cells. The antibody inhibited cell-mediated lympholysis in the absence of complement, while antibody F3-20-7 directed at the canine Thy 1 antigen did not. It was not possible to precipitate a corresponding cell surface antigen on canine cells using standard 125I radioimmunoprecipitation techniques nor did the antibody cause antigenic modulation. Our data suggest that monoclonal antibody T811 reacts with a functional subset of canine T-lymphocytes similar to that of human cells; however, significant differences may exist between the antigens recognized on these cells in the two species.

Animals↗

PubMed1999

Immunological analysis of beta-thalassemic mouse intestinal proteins reveals up-regulation of sucrase-isomaltase in response to iron overload.

Maintenance of iron homeostasis must balance the demand for iron due to heme synthesis, which is driven by hematopoiesis, and the restricted intestinal uptake of iron, which otherwise limits absorption of this toxic element. The consequences of perturbed iron homeostasis are witnessed in inherited forms of beta-thalassemia in which erythroid hyperplasia results in enhanced intestinal iron absorption despite tissue iron overload. To gain a better understanding of intestinal factors that are induced when iron homeostasis is disrupted, a panel of monoclonal antibodies that recognize intestinal microvillous membrane proteins of the beta-thalassemic Hbbd(th3)/Hbbd(th3) mouse was established. The monoclonal antibodies were screened by differential Western blotting against normal and beta-thalassemic mouse intestine to identify antigens modulated in the disease state. Here we report the initial characterization of one immunoreactive species that is up-regulated in beta-thalassemic mouse intestine and the tentative identification of this antigen as sucrase-isomaltase. Studies in Caco-2 cells revealed the rather unexpected finding that expression of this intestinal hydrolase is increased in response to iron toxicity.

Animals↗

PubMed1985

Mb1, a plasma membrane antigen selectively expressed by U-937 cells.

To examine the plasma membrane characteristics of an immature monocytic cell capable of proliferation, we have developed a murine monoclonal antibody that identifies an antigen, Mb1, found on the surface of U-937. In immunofluorescence analyses, Mb1 is not expressed by peripheral blood monocytes (freshly isolated, lymphokine-activated, or cultured for seven days), neutrophils, or any other circulating element. It is also absent on human bone marrow mononuclear cells, including the CFU-GM. Among a series of malignant cells from 50 patients with acute myeloid leukemia (including 22 with monocytic or myelomonocytic leukemia), no Mb1 expression was detected. Continuous human cell lines of B or T cell origin were also negative, as were the myeloid lines HL-60 and K562. Apart from U-937, which uniformly expresses Mb1 in high antigen density, only KG-1 (a myeloblastic line) exhibits Mb1 in low antigen density. Exposure of U-937 to phorbol diester (TPA) under conditions that induce features of macrophage differentiation (including the expression of Mo1) results in a significant reduction in Mb1 expression. Mb1 expression is also reduced as a result of culture of U-937 in medium containing anti-Mb1 antibody (antigenic modulation). On sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radiolabeled immunoprecipitates, Mb1 appears to be a dimeric protein with an estimated molecular weight of 80 kd (43 kd under reducing conditions). Antigenic activity on U-937 is destroyed by treatment with trypsin or papain but is regenerated after 24 hours' culture in enzyme-free medium. Mb1 is a constituent plasma membrane protein of U-937, and its degree of expression relates to the state of cellular differentiation.

Antibodies, Monoclonal↗

PubMed1994

Structural properties of a subset of nephritogenic anti-DNA antibodies.

Structural analysis of lupus autoantibodies is beginning to provide clues to the molecular basis for antigenic specificity and pathogenicity. The present analysis indicates that multiple light and heavy chains contain residues which can facilitate DNA binding, reaffirming the notion that there are multiple ways that different amino acids combine to form an antigen-binding pocket with affinity for dsDNA and ssDNA. Furthermore, this analysis suggests that these conformations and contact residues are intrinsic to germline sequences, although amino acid changes at critical locations (somatically introduced) modulate antigen binding, and appear to influence the capacity of individual immunoglobulin to form immune deposits. Analysis of additional individual immunoglobulins with closely related V-region sequences and differing pathogenic properties will be required to resolve the contribution of specific motifs to pathogenecity.

Amino Acid Sequence↗

PubMed1979

Antigenic characteristics of normal and malignant human hematopoietic cells. Potential use of antigenic differences in cell separation and marrow transplantation.

Recent studies using cytotoxic and cell separation techniques have identified differentiation-related antigens on human hematopoietic cells. These results, combined with bone marrow transplantation studies, have yielded a picture of antigenic modulation from the pluripotent hematopoietic stem cell through the differentiated end cells.

Antigens, Surface↗

PubMed1985

Inner acrosomal membrane of mammalian spermatozoa: its properties and possible functions in fertilization.

The inner acrosomal membrane (IAM) develops during the spermatid stage of differentiation as that portion of the Golgi-derived acrosome granule that tightly associates with the condensing sperm nucleus. In some mammalian species, an electron-dense proteinaceous material accumulates between the IAM and the nuclear envelope, collectively comprising the "perforatorium." Evidence, including its partial purification and its structural resistance to detergents and sonication, suggests that the IAM is an unusually resiliant membrane. Dense paracrystalline arrays of intramembranous particles, a lack of lectin-mediated receptor modulation, and its lack of participation in sperm-egg fusion suggest that the IAM lacks the same degree of fluidity as the egg surface plasmalemma. Observations using monoclonal antibodies, however, suggest that some specific antigenic modulations may be possible within the IAM. Its structural rigidity is of obvious mechanical value during sperm penetration through the zone pellucida. An additional role as a scaffold for putative zona lysin material remains controversial. Biochemical evidence suggests that acrosin, for example, is not entirely soluble and that some remains sperm-associated, depending on the conditions of acrosome disruption. Nevertheless, morphological studies do not agree on acrosin's specific localization to the IAM. Currently there is only very limited information concerning the localization of the other acrosomal enzymes to the IAM. Another possible role for the IAM in some species may be in recognizing the zona pellucida. Evidence for this derives from the observation that fucoidin, a fucose heteropolysaccharide, inhibits guinea pig sperm-zona binding, and bound fucoidin can be localized to the IAM and equatorial regions of the living acrosome-reacted spermatozoa. Finally, the IAM may have a role in early recognition/adhesion with the colemma.

Acrosome↗

PubMed1992

Glycosyl-phosphatidylinositol-anchored membrane proteins.

Many proteins of eukaryotic cells are anchored to membranes by covalent linkage to glycosyl-phosphatidylinositol (GPI). These proteins lack a transmembrane domain, have no cytoplasmic tail, and are, therefore, located exclusively on the extracellular side of the plasma membrane. GPI-anchored proteins form a diverse family of molecules that includes membrane-associated enzymes, adhesion molecules, activation antigens, differentiation markers, protozoan coat components, and other miscellaneous glycoproteins. In the kidney, several GPI-anchored proteins have been identified, including uromodulin (Tamm-Horsfall glycoprotein), carbonic anhydrase type IV, alkaline phosphatase, Thy-1, BP-3, aminopeptidase P, and dipeptidylpeptidase. GPI-anchored proteins can be released from membranes with specific phospholipases and can be recovered from the detergent-insoluble pellet after Triton X-114 treatment of membranes. All GPI-anchored proteins are initially synthesized with a transmembrane anchor, but after translocation across the membrane of the endoplasmic reticulum, the ecto-domain of the protein is cleaved and covalently linked to a preformed GPI anchor by a specific transamidase enzyme. Although it remains obscure why so many proteins are endowed with a GPI anchor, the presence of a GPI anchor does confer some functional characteristics to proteins: (1) it is a strong apical targeting signal in polarized epithelial cells; (2) GPI-anchored proteins do not cluster into clathrin-coated pits but instead are concentrated into specialized lipid domains in the membrane, including so-called smooth pinocytotic vesicles, or caveoli; (3) GPI-anchored proteins can act as activation antigens in the immune system; (4) when the GPI anchor is cleaved by PI-phospholipase C or PI-phospholipase D, second messengers for signal transduction may be generated; (5) the GPI anchor can modulate antigen presentation by major histocompatibility complex molecules. Finally, at least one human disease, paroxysmal nocturnal hemoglobinuria, is a result of defective GPI anchor addition to plasma membrane proteins.

Amino Acid Sequence↗

PubMed1989

Lung injury in rabbits induced by intravenous administration of heterologous polyclonal antibodies to angiotensin converting enzyme (kininase II).

Antibody interactions with the endothelial cell membrane glycoprotein angiotensin converting enzyme (Kininase II) in vivo exhibit features of aggregation and capping with resultant shedding similar to those events described in several in vitro isolated cell systems. Requirements for divalent ligand binding, deposition of complement and participation of cytoskeletal elements are demonstrated in vivo. Persistence of antigen in immune complexes with complement interaction appear to be necessary to induce an inflammatory response. Abrogation of this response occurs when circumstances permit antigenic modulation with removal of the immune complex from the endothelial surface.

Animals↗

PubMed1986

Round cell variant of measles virus: neurovirulence and pathogenesis of acute encephalitis in newborn hamsters.

A subacute sclerosing panencephalitis (SSPE) strain of measles virus has been previously shown to be composed of two interrelated but separable viral variants. One of these, the syncytiagenic or S variant, resembles defective, cell-associated strains of measles virus; while the other, the round cell inducing or RC variant, induces a highly productive infection in cell culture. It is now reported that the S variant is more neurovirulent in newborn hamsters than the RC variant and that viral replication in infected CNS tissues occurs in two phases. Early in the infection cell-free virus, composed primarily of the RC variant, is produced. Later, coincident with the appearance of antiviral antibody, cell-free virus rapidly disappears, leaving behind only cell-associated virus which resembles the S variant. Quantification of viral antigen expression in the infected tissues suggests that this change in the state of infection is not associated with antigenic modulation, but rather is the result of preferential elimination of RC variant infected cells.

Acute Disease↗

PubMed1985

Influence of dendritic cells on tumor growth.

Dendritic cells (DC) exposed to antigen are potent initiators of immune responses, and the numbers of DC and the dose of antigen control the level of response. The influence of these variables was tested on the growth of mouse sarcoma cells in vivo. When normal syngeneic DC (100,000) were given to mice with palpable tumors, tumor regression or delay in tumor growth was obtained. DC exposed to increasing doses of tumor extract in vitro before administration had progressively less effect. DC exposed to antigen delayed tumor growth significantly only when given on the same day as 500 tumor cells. The studies suggested that low doses of antigen on DC elicit immune responses and that high doses block them. The numbers of antigen-presenting cells and the dose of antigen modulate the degree of immunity to mouse sarcoma in vivo.

Animals↗

PubMed1995

Effects of MHC-encoded TAP1 and TAP2 gene polymorphism and matching on kidney graft rejection.

The products of TAP1 and TAP2 genes, recently mapped within the MHC class II region, are involved in antigen presentation by MHC class I molecules, especially in the transport of endogenous peptides. As for most MHC genes, a polymorphism has been described and the possibility that it could influence the recipient immune response by modulating antigen presentation in kidney transplantation has been tested. The aim of our study was to compare TAP1 and TAP2 gene polymorphism and matching in 53 couples of kidney donors and recipients without any rejection episodes and in 55 other couples who had experienced at least 2 acute cellular rejection episodes; 70 healthy individuals served as controls. Our results showed that allelic variant frequencies of TAP1 alleles (1A to 1C) and TAP2 alleles (2A to 2E), as assessed by amplification refractory mutation system-polymerase chain reaction, were similar among "rejection" and "no rejection" populations. Furthermore, there were no differences of TAP1 and/or TAP2 matching between donors and recipients in the 2 groups. In contrast, we showed that the recipients of the no rejection group were better matched with their corresponding donors for the HLA-DR genes than those of the rejection group. These results suggest that the currently described polymorphism in the limited coding region of TAP1 and TAP2 genes does not influence the incidence of kidney allograft rejection episodes and seems not to be a strong link to the adjacent DR/DQ subregion. Moreover, the observed increase frequency of TAP1B allele in the whole recipient's group as compared with controls (16.2% vs. 7.1% in the healthy individuals; P < 0.02) was not linked to the rejection occurrence but to the presence of glomerulonephritis as initial disease. Our study suggests that, in the clinical conditions tested, neither TAP polymorphism nor TAP matching influences the renal graft outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

The Mycobacterium tuberculosis recombinant 27-kilodalton lipoprotein induces a strong Th1-type immune response deleterious to protection.

Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

Animals↗

PubMed1988

Development of an antigen-specific CD8 suppressor effector clone in man.

A long-term cultured IL-2-dependent keyhole limpet hemocyanin (KLH)-specific CD8 (T8) suppressor clone (5B9) was generated from a healthy donor hyperimmunized with KLH. The 5B9 clonal population suppressed in vitro anti-KLH antibody response but did not suppress anti-TT antibody response or PWM-driven IgG synthesis. Moreover, 5B9 cells could not suppress anti-TT antibody response even in the presence of free KLH. 5B9 cloned cells suppressed the anti-KLH antibody response of B cells cultured with CD4+4B4+ cells without requiring the presence of CD8+ cells. This KLH-specific CD8 suppressor clone is an effector type rather than an inducer type of suppressor T cell. The cloned cells expressed alpha- and beta-TCR proteins (defined by WT-31 antibody) on their cell surface. More importantly, the CD3:TCR complex was functionally important in the suppression induced by this clone, because after CD3 antigen modulation from its cell surface, the suppressor effector function was abolished.

Adjuvants, Immunologic↗

PubMed1985

Cloning of Bordetella pertussis outer membrane proteins in Escherichia coli.

We have cloned in Escherichia coli a 40 kb chromosomal DNA fragment of Bordetella pertussis which encoded the synthesis of two major outer membrane proteins specific to this microorganism. The clone harbouring the plasmid pFSH200 has shown modulation of the expression of these proteins when grown on complete solid medium. However, this phenomenon has not occurred in clones harbouring smaller derivatives of plasmid pFSH200 and one such derivative, plasmid pFSH201, has been isolated and further characterized. These results suggest that the large plasmid pFSH200 contained a regulatory sequence affecting the expression of the outer membrane proteins of Bordetella pertussis in Escherichia coli. This sequence is very likely responsible for the antigenic modulation observed in phase I strains of Bordetella pertussis.

Antigens, Bacterial↗

PubMed1980

Alloantigens of the human T (HT) genetic region of the HLA linkage group.

This article describes an approach that characterizes alloantisera reactive with new determinants on mitogen-activated human lymphocytes. These markers, which are tentatively called HT-antigens, are different from the classical HLA-A,C,C, and DR antigens but are associated with beta 2-microglobulin. Several alloantisera were tested extensively on lymphocytes that were treated initially with an antigen-blocking technique using turkey anti-beta 2-microglobulin and turkey anti-p29,34 sera or with an antigen-modulation technique using xeno- and alloantisera. It was concluded that these tested antisera recognized three different determinants (HT1, HT3, and HT (1 + 3) that appeared to segregate with the HLA-A locus of the HLA haplotype. HT antigens may be analogous to the murine TL-Qa antigens since HT antigens are associated with beta 2-microglobulin, are generally related to the HLA region, and are expressed on mitogen activated T cells but not on resting T cells.

Absorption↗