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 955 records · Page 53Linked to original sources
PubMed1996

Rapid modulation of T lymphocyte surface antigens induced by Fas (CD95, APO-1) ligation.

Crosslinking the Fas (CD95, APO-1) antigen by mAb or Fas-ligand (Fas-L)-expressing cells triggers apoptosis. We have investigated the early consequences of Fas signaling on the expression of various cell surface antigens on T lymphocytes. Incubation of Fas-sensitive Jurkat (JM) cells with agonistic anti-Fas mAb induced rapid (within 4 hr) downmodulation of L-selectin (CD62L) and CD7 but not of CD3 or CD71. No modulation was observed on Fas-expressing but Fas-resistant JM variant 432.1. On PHA-activated, Fas-sensitive T cell blasts, anti-Fas mAb rapidly triggered downmodulation of a variety of antigens, including CD2, CD4, CD8, CD7, CD44, LFA1alpha, LFA1beta, and CD62L, but not CD3, CD25, or CD26. Most of these antigens were not downmodulated by either CD3 crosslinking (except CD3) or PMA treatment (except CD3, CD4, and CD62L). Comparable patterns of biphasic CD44, LFA1alpha, and LFA1beta expression were observed on CD4+ and CD8+ T cell blasts in response to Fas crosslinking. In these instances, downregulation occurred preferentially on cells undergoing rapid shrinkage. These results indicate that rapid downregulation of selected surface antigens is an early response of both normal and transformed T cells to Fas crosslinking.

Antigens, CD↗
PubMed2001

Multivalent DNA-based immunization against hepatitis B virus with plasmids encoding surface and core antigens.

The immune response against hepatitis B surface and core antigens was evaluated by either coinoculation or independent intramuscular administration of pAEC compact DNA immunization vectors carrying their genes. The pAEC vectors bear just the essential elements for mammalian expression and bacterial amplification. Balb/c mice were immunized with 100 microg of each construct, either alone or in combination. In spite of lacking known immunostimulatory sequences (e.g., AACGTT), significant cellular (proliferative) and humoral immune responses were raised against both antigens. Coadministration of both plasmids maintained the immune response against the two antigens, without interference between them. Modulation of the antigen expression and further immune response, by using the Kozak's translation initiation sequence, was also analyzed. No differences due to its presence or absence were observed.

Animals↗
PubMed1997

CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics.

The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (Kd values approximately 12 and approximately 200 nM, respectively) that are high when compared with other molecular interactions that contribute to T cell-APC recognition. In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4. At 37 degrees C, soluble recombinant CD80 bound to CTLA-4 and CD28 with Kd values of 0.42 and 4 microM, respectively. Kinetic analysis indicated that these low affinities were the result of very fast dissociation rate constants (k(off)); sCD80 dissociated from CD28 and CTLA-4 with k(off) values of > or = 1.6 and > or = 0.43 s-1, respectively. Such rapid binding kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate-dynamic T cell-APC contacts and to facilitate scanning of APC for antigen.

Abatacept↗
PubMed1988

Pox viruses as eukaryotic cloning and expression vectors: future medical and veterinary vaccines.

It was proposed at the beginning of this article that the use of poxviruses as expression vectors provided a means of optimizing the conditions and prerequisites of vaccination and of elucidating a number of the associated problems. These advantages will now be summarized. Vaccinia virus recombinants carrying one or more multiple foreign genes have been shown to induce a sufficient immune response to that antigen in laboratory animals to protect against subsequent challenge by the infectious agent. In those animals tested the duration of immunity has been long-lasting with no apparent detrimental side-effects. Vaccinia virus is very stable in normal environmental situations and no cold-chain is required in the distribution network. There is no evidence for genetic instability of the vaccinia 'carrier' strain nor of loss of the inserted genetic elements. The vaccine is administered intradermally and it is proposed that one inoculation will be sufficient to induce immunity to multiple disease antigens; however, re-inoculation at a later time with the same or new antigenic determinants is not precluded. The efficiency of vaccinia virus as the vaccine strain used to eliminate the disease of smallpox with minimal side-effects is well documented. The recent studies described here on the development of vaccinia as a viral vector confer other advantages. Since the expression of the inserted genetic element is under vaccinia virus control, different levels of expression can be engineered by substituting the promoter sequence placed proximal to the insert. This leads to the possibility of high levels of expression when required for a single antigen or more modulated levels when multiple foreign antigens are expressed and 'genetic overload' could become a problem. Much work remains to be done on the body's immune response to this proposed genetic intrusion. The ability to insert large amounts of genetic information without disrupting virus replication and assembly indicates a great degree of flexibility in the genome strategy of the virus. This may indicate that the replication system can be further disrupted to eliminate or modify those sequences coding for virulence and wide host range to make the poxvirus vector as safe as possible for vaccine use. One of the reasons traditional vaccine strategy has failed for some virus groups is the degree of variability found in virus strains in nature. Influenza viruses are a good example, as are the bluetongue virus group, rotaviruses and bunyaviruses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Generation of stable cellular phenotypes in a human malignant cell line conditioned by alterations in the cellular microenvironment.

Microenvironmental conditions may result in phenotypic changes of malignant cells and/or selection of preexisting variants with a growth advantage under the new growth conditions. The present study was initiated to evaluate the stability of changes in crucial cellular attributes as induced in vivo by nonimmunological mechanisms. Expression of major histocompatibility antigens, membrane immunoglobulin, in vitro growth rate, chromosome complement, and modal chromosome number were thus examined in a human B-lymphoma line (RH-L4) prior to and after short-term passage through the peritoneal cavity or spleen of newborn mice. Seven sublines (four from spleen and three from peritoneal cavity) of RH-L4 cells were established after the passage. These lines were found to differ phenotypically from the original line in respect to several or all of the attributes that were studied. These differences were stable for greater than 100 cell generations. Analyses of major histocompatibility complex Class II antigen expression indicated that the modulation of this antigen was independent of the immunological competence of the mice and unrelated to cell cycle-dependent variations. The emergence of the variant sublines seemed not to reflect a microenvironmentally determined selection of minority subpopulation in the original RH-L4 lymphoma line but, instead, induced by the growth conditions in the cellular microenvironment in the mouse. It is suggested that inductive processes may be of importance in the generation of phenotypic diversity within individual tumor cell populations, including the generation of phenotypic variants with high metastatic activity.

Animals↗
PubMed1979

Enhancement of carcinoembryonic antigen expression by interferon.

Human interferon decreased DNA but not RNA synthesis in a human colon carcinoma cell line, WiDr; in addition, there was a two- to three-fold increase in the expression of a tumor-associated antigen, carcinoembryonic antigen. In contrast, interferon had no effect on a normal human diploid cell line, WI-38. Thus, in addition to its anti-cellular effect against tumor cells, interferon can also modulate tumor antigenicity.

Carcinoembryonic Antigen↗
PubMed1992

The effect of retinal autoantigens and their peptides on the inhibition of experimental autoimmune uveitis.

Experimental autoimmune uveitis is an immune-mediated inflammation of the retina and uveal tract. Such inflammation can be induced in eyes of experimental animals by inoculating them with retinal autoantigens. This animal model of uveitis closely resembles idiopathic uveitis in humans and lends itself ideally for the study of mechanisms involved in the aetiopathogenesis of uveitis and for the evaluation of methods used to control or prevent immune-mediated intraocular inflammation. In this study we used the retinal proteins S-antigen, interphotoreceptor retinoid binding protein and some synthetic peptides of S-antigen to modulate the immune response of Lewis rats. Following immunomodulation these animals did not develop uveitis when challenged with the retinal proteins. The discovery of small, non-pathogenic peptides of retinal antigens that down-regulate the immune response has relevance in developing strategies for immune intervention in human uveitis.

Amino Acid Sequence↗
PubMed2002

Induction of the rainbow trout MHC class I pathway during acute IHNV infection.

Interferons are essential for establishing cytotoxic T-lymphocyte immunity against viral pathogens through different mechanisms including the modulation of antigen presentation to T-cell subsets. At the present time, interferons have yet to be isolated from teleost fish. We have developed a salmonid model to examine whether MHC gene regulation is modulated during acute viral infection in trout, an event attributable to interferons in mammals. During peak infection with infectious hematopoietic necrosis virus, induction of STAT-1, PSMB9A and ABCB2 mRNA was evident in all tissues within infected fish, as compared with controls. In addition, MHC class Ia and beta(2) microglobulin (beta(2)m) transcript levels were enhanced within the experimental group but surprisingly, splenic and pronephric class IIB mRNA expression was virtually absent. A time-course study looking at 24, 72 and 192 h post-infection was then performed to determine the overall kinetics of this response. STAT-1 and PSMB9A message levels increased early during the immune response and remain at relatively high levels until the final time point. MHC class Ia expression is not consistently upregulated until midway in the response. MHC class IIB transcripts are downregulated by 72 h in the spleen and pronephros and then partially restored by 192 h. Finally, analysis of the putative promoter regions for PSMB9A and ABCB2 identified interferon (IFN) regulatory factory (IRF-1) and INF-gamma (GAS) activation sites that may be involved in the regulation of these genes during viral infection.

Animals↗
PubMed2003

Trypanosoma cruzi infection: a continuous invader-host cell cross talk with participation of extracellular matrix and adhesion and chemoattractant molecules.

Several lines of evidence have shown that Trypanosoma cruzi interacts with host extracellular matrix (ECM) components producing breakdown products that play an important role in parasite mobilization and infectivity. Parasite-released antigens also modulate ECM expression that could participate in cell-cell and/or cell-parasite interactions. Increased expression of ECM components has been described in the cardiac tissue of chronic chagasic patients and diverse target tissues including heart, thymus, central nervous system and skeletal muscle of experimentally T. cruzi-infected mice. ECM components may adsorb parasite antigens and cytokines that could contribute to the establishment and perpetuation of inflammation. Furthermore, T. cruzi-infected mammalian cells produce cytokines and chemokines that not only participate in the control of parasitism but also contribute to the establishment of chronic inflammatory lesions in several target tissues and most frequently lead to severe myocarditis. T. cruzi-driven cytokines and chemokines may also modulate VCAM-1 and ICAM-1 adhesion molecules on endothelial cells of target tissues and play a key role in cell recruitment, especially of activated VLA-4+LFA-1+CD8+ T lymphocytes, resulting in a predominance of this cell population in the inflamed heart, central nervous system and skeletal muscle. The VLA-4+-invading cells are surrounded by a fine network of fibronectin that could contribute to cell anchorage, activation and effector functions. Since persistent "danger signals" triggered by the parasite and its antigens are required for the establishment of inflammation and ECM alterations, therapeutic interventions that control parasitism and selectively modulate cell migration improve ECM abnormalities, paving the way for the development of new therapeutic strategies improving the prognosis of T. cruzi-infected individuals.

Animals↗
PubMed1991

Human melanoma-associated antigen expression on human neuroblastoma cells: effects of differentiation inducers.

We have described two human melanoma-associated antigens (HMAA), recognized by the murine monoclonal antibodies LS62 and LS109. LS62 recognizes the neuroglandular antigen (NGA), which is overexpressed in neoplastic melanocytes as well as in several tissues of neuroectodermal origin. These antibodies were used to screen six neuroblastoma cell lines and one neuroepithelioma cell line. A melanoma cell line, G361, known to express the two antigens, was used as the positive control. Variable expression of the two antigens was detected in neuroblastoma cells. The surface expression of NGA and of the LS109 antigen was modulated in parallel with the morphological differentiation induced by retinoic acid, 5-bromodeoxyuridine, or cyclic AMP analog/activators. The modulation of the expression of the two HMAA was detected in G361 melanoma cells and in one of the neuroblastoma cell lines, SK-N-SH. These results suggest altered expression of both antigens during melanoma and neuroblastoma cell differentiation in culture.

Animals↗
PubMed2005

Th2-type immune response observed in healthy individuals to sonicate antigen prepared from the most prevalent Mycobacterium tuberculosis strain with single copy of IS6110.

Different Mycobacterium tuberculosis strains operate different immune evasion strategies for their survival in the host. This mainly depends on the virulence of the strain and the host immune responses. The most virulent strains are actively involved in the transmission, widely spread in the community and induce differential immune responses. We evaluated the immune response of a sonicate antigen prepared from one predominant strain (S7) from M. tuberculosis harbouring a single copy of IS6110. Significant lymphoproliferative response against purified protein derivative from tubercle bacillus (PPD) and H37Rv antigens was observed in PPD positive normal individuals and tuberculosis patients. Interferon-gamma (IFN-gamma) levels against these antigens were significantly increased in normal individuals but not in tuberculosis patients. The antigen S7 showed marginal T-cell proliferation but did not induce IFN-gamma secretion in both groups. Conversely, it induced significantly high levels of cytokine interleukin 4 (IL-4) in normal individuals. The macrophage cytokines, IL-12 and tumour necrosis factor alpha (TNF-alpha), did not show S7 antigen specific stimulation. The intracellular cytokine further confirmed an increase in IL-4(+)/CD4+ T-cells and a decrease in IFN-gamma(+)/CD4+ T-cells upon stimulation. The antibody response showed an increase in IgG and IgA levels against this antigen in normal individuals. These observations suggest that antigen S7 modulates the immune response towards T helper cell type 2 by suppressing T helper cell type 1 protective immune response in PPD positive normal individuals. We speculate that some components of this sonicate antigen are associated with immunosuppressive response.

Adult↗
PubMed1999

Molecular basis for Rh(null) syndrome: identification of three new missense mutations in the Rh50 glycoprotein gene.

Rh(null) is a rare autosomal recessive disorder characterized by an absence of Rh antigens and a varying degree of hemolytic anemia and spherostomatocytosis. We report studies of two Japanese Rh(null) cases and describe three new missense mutations of RHAG, the locus that encodes Rh50 glycoprotein and modulates Rh antigen expression. In Rh(null)(HT), RHAG harbored in exon 6 two G-->A transitions, GTT-->ATT and GGA-->AGA, which cause Val(270)-->Ile and Gly(280)-->Arg substitutions, respectively. These missense mutations were cotransmitted from the propositus to the children and were predicted to reside in endoloop 5 and transmembrane (TM) segment 9, respectively. In Rh(null)(WO), RHAG contained in exon 9 a single G-->T transversion, GGT-->GTT, which caused a Gly(380)-->Val missense change in TM12 segment. The G-->T transversion, which is located at the +1 position of exon 9, had also affected pre-mRNA splicing and caused partial exon skipping. Although both Rh(null) cases had a structurally normal RH antigen locus, hemagglutination and immunoblotting showed no expression of Rh antigens or proteins. These results correlate each mutation with a structural defect in the respective TM domain of Rh50 glycoprotein.

Amino Acid Sequence↗
PubMed2002

Evaluation of a new combined antigen and antibody human immunodeficiency virus screening assay, VIDAS HIV DUO Ultra.

Combined antigen and antibody screening (fourth-generation) assays reduce the diagnostic window period between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis by 4 days, on average, in comparison to antibody-only (third generation) enzyme immunoassays (EIAs). The aim of the present study was to assess whether the new VIDAS HIV DUO Ultra (Biomérieux, Marcy-l'Etoile, France) showed an improved sensitivity and specificity in comparison to licensed fourth-generation assays. A total of 16 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 257 potentially cross-reactive serum samples were tested with VIDAS DUO HIV Ultra, Genscreen Plus HIV Ag-Ab, Enzygnost HIV Integral, Enzymun-Test HIV Combi, Genscreen HIV 1/2, version 2 (third-generation EIA), and Genetic Systems HIV-1 Ag EIA (p24 antigen assay). VIDAS HIV DUO Ultra showed a comparable sensitivity to the single p24 antigen assay in seroconversion panels and a dilution series of virus lysates. The diagnostic window was reduced with VIDAS HIV DUO Ultra by 3.82 days, on average, in comparison with the fourth-generation assay with the lowest sensitivity of the antigen detection module. HIV-1 infection was detected 5.88 days earlier than with third-generation EIA. The mean time delay between reverse transcription-PCR and VIDAS HIV DUO Ultra was only 2.31 days. The specificity of fourth-generation assays after retesting ranged between 98.1 and 100%. In conclusion, VIDAS HIV DUO Ultra can replace single-antigen screening for laboratory diagnosis and screening of HIV infection in blood donors. There was no evidence for a second diagnostic window due to impaired sensitivity of the antibody detection module of all the fourth-generation EIAs evaluated in the present study. The specificity after initial and/or repeated testing of VIDAS HIV DUO Ultra was equivalent to that of a third-generation assay.

AIDS Serodiagnosis↗
PubMed1995

HLA-DRB1 molecules and antigenic experience shape the repertoire of CD4 T cells.

Forces influencing the composition of the mature TCR repertoire have been well studied in the mouse. In particular, the contribution of MHC molecules in negative and positive selection events of T lymphocytes has been established. To understand whether the allelic polymorphism of HLA-DRB1 molecules can shape the human TCR repertoire, we compared the usage of TCR V beta segments in two cohorts of unrelated individuals who were selected for the expression of HLA-DRB1 alleles. To investigate the potential role of antigenic experience in shaping the TCR repertoire, we compared the usage of V beta gene elements in CD45RO- CD4+ (naive) T cells versus CD45RO+ CD4+ (memory) T cells. A correlation between V beta gene segment usage and HLA-DRB1 alleles could be demonstrated for the repertoire of the naive CD4+ T cells, suggesting a shaping force of the HLA-DRB1 allele on the peripheral TCR repertoire. While the HLA-DRB1 imposed profile in V beta distribution was maintained in CD45RO+ CD4+ T cells, it was less pronounced, indicating that antigenic experience modulates the functional TCR repertoire.

Alleles↗
PubMed2006

The mouse immune response to carrier erythrocyte entrapped antigens.

This study investigated the potential of a single administration of carrier erythrocyte entrapped antigen to elicit humoral responses in the Balb/c mouse. Humoral responses to primary immunizations of erythrocyte encapsulated antigens were compared with those obtained with adjuvanted antigen administered via the subcutaneous route. Ig isotype responses to primary immunizations of erythrocyte entrapped antigen and subcutaneous antigen were compared to responses observed in mice that subsequently received booster immunizations with un-entrapped antigen. This study demonstrates that a single administration of antigen-loaded carrier erythrocytes is able to elicit humoral immune responses comparable or superior to those obtained via the adjuvanted subcutaneous vaccination route. The IgG isotype profiles demonstrate that the erythrocyte entrapment of antigens is another mechanism by which the Th responses to antigens maybe modulated.

Animals↗
PubMed1994

Expression and modulation of CD44 variant isoforms in humans.

CD44 is a ubiquitous surface molecule that exists as a number of isoforms, generated by alternative splicing of 10 "variant" exons. Little is known about the expression and function of the variant isoforms, except that certain isoforms may play a role in cancer metastasis. We produced mAbs against CD44 variant regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein spanning variant exons 3v to 10v. A comprehensive analysis of human tissues revealed that CD44 variant isoforms were expressed widely throughout the body, principally by epithelial cells. However there was differential expression of CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but much fewer expressed 6v or 4v. The regions of epithelia that expressed the highest levels of the variant isoforms were the generative cells, particularly the basal cells of stratified squamous epithelium, and of glandular epithelium. CD44 variant isoforms were also expressed differentially by leukocytes, with CD44-9v expressed at very low levels and CD44-6v and 4v virtually absent. However, CD44-9v and CD44-6v were the main variants that were transiently upregulated on T cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha and IFN gamma treatment. Some epithelial cell lines could preferentially upregulate CD44-6v upon IFN gamma incubation. These results show that CD44 variant isoforms are expressed much more widely than first appreciated, and that expression of the variant isoforms on some cell types can be modulated by particular cytokines.

Amino Acid Sequence↗
PubMed2005

Mutational escape from CD8+ T cell immunity: HCV evolution, from chimpanzees to man.

The mechanisms by which the hepatitis C virus (HCV) establishes persistence are not yet fully understood. Previous chimpanzee and now human studies suggest that mutations within MHC class I-restricted HCV epitopes might contribute to viral escape from cytotoxic T lymphocyte (CTL) responses. However, there are several outstanding questions regarding the role of escape mutations in viral persistence and their fate in the absence of immune selection pressure.

Animals↗