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Results for “Receptors, Pattern Recognition”

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PubMedDate not supplied

Lesion-derived low density lipoprotein and oxidized low density lipoprotein share a lability for aggregation, leading to enhanced macrophage degradation.

In this study we assessed whether low density lipoproteins (LDL) isolated from minced aortic atherosclerotic plaques obtained at autopsy (A-LDL) shared structural and functional properties with LDL oxidized by incubation with Cu2+ for 8-18 hours at 20 degrees C (Ox-LDL). Although both A-LDL and Ox-LDL represented monomeric particles about the size of LDL, both differed from LDL in that they showed an increase in electrophoretic mobility relative to LDL, an increase in cholesterol to protein ratio, and an increase in reactivity with a monoclonal antibody that recognizes epitopes on malondialdehyde (MDA)-modified proteins. In addition, both showed an increase in fluorescence at 360 nm excitation, 430 nm emission, an increase in fragmentation of apolipoprotein B with patterns that were quite similar, and an increase in recognition by the scavenger receptor on mouse peritoneal macrophages (MPMs) based on competition of 125I-A-LDL and 125I-Ox-LDL degradation by excess acetylated LDL. In addition, inhibition of degradation by MPMs of 125I-A-LDL and 125I-Ox-LDL by excess unlabeled Ox-LDL and A-LDL were similar. When MDA was added in increasing amounts to labeled LDL and A-LDL, less MDA was required to modify A-LDL than LDl to obtain ligands that were degraded by MPMs to the same degree. Finally, both A-LDL and Ox-LDL but not LDL underwent aggregation (increased metastability) when concentrated to levels exceeding 1 mg protein/ml and showed enhanced macrophage uptake via phagocytosis (inhibition by cytochalasin D). These results demonstrate that A-LDL and Ox-LDL share properties additional to those previously reported, suggesting that oxidation may be a major mode of modification of LDL accumulating in atherosclerotic lesions. This could lead to lipid loading of macrophages induced by phagocytosis of aggregated particles, in addition to unregulated uptake via the scavenger receptor of monomeric particles.

Acetylation↗

PubMed2005

Immunoregulation of dendritic cells.

The paradigm of tolerogenic/immature versus inflammatory/mature dendritic cells has dominated the recent literature regarding the role of these antigen-presenting cells in mediating immune homeostasis or self-tolerance and response to pathogens, respectively. This issue is further complicated by the identification of distinct subtypes of dendritic cells that exhibit different antigen-presenting cell effector functions. The discovery of pathogen-associated molecular patterns and toll-like receptors provides the mechanistic basis for dendritic cell recognition of specific pathogens and induction of appropriate innate and adaptive immune responses. Only recently has insight been gained into how dendritic cells contribute to establishing and/or maintaining immunological tolerance to self. Soluble and cellular mediators have been reported to effectively regulate the function of dendritic cells by inducing several outcomes ranging from non-inflammatory dendritic cells that lack the ability to induce T lymphocyte activation to dendritic cells that actively suppress T lymphocyte responses. A thorough discussion of these stimuli and their outcomes is essential to understanding the potential for modulating dendritic cell function in the treatment of inflammatory disease conditions.

Animals↗

PubMed1987

T cell receptor beta chain gene rearrangements and V beta gene usage in horse cytochrome c-specific T cell hybridomas.

Comparison of T cell receptor alpha and beta-chain genes in murine major histocompatibility complex (MHC) class I and class II-restricted T cell clones and hybridomas recognizing different antigens indicates that no simple correlation exists between the observed antigen/MHC specificity and the expression of certain alpha and beta-chain heterodimers. We have attempted to establish a possible correlation by analyzing T cell receptor beta chain gene rearrangements and V beta gene usage in five T cell hybridomas with identical antigen/MHC specificity and another hybridoma recognizing a different antigenic determinant in association with the same restriction molecule. We report here that in each of the five clones a uniquely rearranged beta chain gene is expressed in combination with at least two different V beta gene segments. The presence of the differently rearranged T cell receptor beta chain genes correlated with the finding of distinct fine specificity pattern of antigen recognition in each of the hybridomas. Interestingly, two hybridomas specific for different epitopes showed identical beta chain D-J rearrangements indicating that the differences might be encoded by the alpha chain gene or/and the V beta gene element.

Animals↗

PubMed2004

Complement receptors and the shaping of the natural antibody repertoire.

Complement and complement receptors have been known for several decades to play important roles in immune effector mechanisms related to pathogen elimination and tissue inflammation. In addition, studies over the last 10 years have clearly demonstrated a key role for the complement C3d activation fragment receptor designated CR2 (complement receptor type 2) in the switched-isotype, high-affinity and memory humoral immune responses to T-dependent foreign antigens. More recent studies have extended those observations to include a key role for CR2 and C3d in the humoral immune response to T-independent foreign antigens. Conversely, as these studies have proceeded, a parallel series of analyses have linked defects in expression or function of complement C4 and other classical pathway activation pathway proteins, as well as CR2 and the closely related CR1, to the loss of self tolerance to nuclear antigens such as double-stranded DNA and chromatin in systemic lupus erythematosus. With regard to the topic of this issue, it is now becoming increasingly clear that CR2 also plays a major role in the development of the natural antibody repertoire. Specifically, in the absence of this receptor natural IgM and IgG develop in the naïve animal that demonstrate clearly altered recognition patterns for specific natural antibody targets. This repertoire change is important physiologically in at least one setting because these CR2-dependent natural antibodies are necessary for the recognition of ischemic self tissues. In addition, it is possible that certain of the phenotypes manifest by CR2-deficient mice may be strongly influenced not only by effects on later stages of B cell activation and maturation, as commonly thought, but also by alterations in the pre-existing pool of natural antibodies that are influenced by this receptor. This review will examine the evidence that has accumulated over the last few years supporting these hypotheses.

Animals↗

PubMed2004

Role of Toll-like receptor 4 in the initiation and progression of atherosclerotic disease.

The family of Toll-like receptors (TLRs) initiates an innate immune response after recognition of pathogen-associated molecular patterns (PAMPs). Evidence is accumulating that TLRs, and particularly TLR4, are important players in the initiation and progression of atherosclerotic disease. Not only exogenous ligands but also endogenous ligands that are expressed during arterial injury are recognized by TLR4. Mouse knockout studies and epidemiological studies of human TLR4 polymorphisms have demonstrated that the TLR4 might play a role in the initiation and progression of atherosclerosis. This review will summarize the latest progression in research on the role of TLR4 in arterial occlusive disease In addition, the potential of intervention in TLR4 signalling to influence progression of atherosclerotic disease is discussed.

Animals↗

PubMed1999

Diverse T-cell receptor CDR3 length patterns in human CD4+ and CD8+ T lymphocytes from newborns and adults.

T cells are essential in the initiation and maintenance of immune responses. Specific interaction between T cells and a presumptive antigen occurs through recognition of an MHC-peptide complex by the T-cell receptor (TCR). The complementarity-determining region (CDR) 3 of the TCR has direct contact with the peptide. Here we describe CDR3 length variability of six different TCRBV gene families of CD4+ and CD8+ umbilical cord (UC) and peripheral blood (PB) T cells. Amplified products spanning the TCR CDR3 regions from CD4+ PB, CD4+ UC and CD8+ UC blood T cells typically displayed Gaussian-like distributions. In contrast, profound and frequent perturbations were recorded in CD8+ PB lymphocytes, with a non-Gaussian pattern in more than half of the samples studied. A substantial portion of the perturbed CD8+ subsets were clonal or oligoclonal, as determined by CDR3-length restriction, TCRBJ gene usage and nucleotide sequencing. This implies that the conditions for shaping and maintenance of the peripheral TCR repertoire are profoundly different for CD8+ and CD4+ T cells.

Adult↗

PubMed1994

Recombinant receptors as probes for the study of genetic stability.

Membrane receptors coupled to GTP binding G-proteins constitute one of the largest families of proteins involved in ligand binding, signal transmission and modulation of physiological effects. A large majority of current pharmaceuticals are actually ligands for this type of receptor, including e.g. the catecholamine, dopamine, serotonin and histamine antagonists. In recent years, an impressive number of the genes encoding these receptors have been cloned, sequenced and expressed in model cell lines. Molecular genetics has thus uncovered the existence of a surprisingly large number of homologous receptor subtypes each capable of binding the same natural ligand, but which may be distinguished on the basis of variable recognition patterns of synthetic ligand panels, variable expression during development and differentiation or different G-protein coupling and effector modulation. We have summarized in Table 1 some of the recently cloned receptors and have attempted to group them according to the type of ligand recognized: non peptidic, peptidic or other, including light and olfactory substances. Further information and references can be found in recent reviews.

Animals↗

PubMed2000

In a novel form of IFN-gamma receptor 1 deficiency, cell surface receptors fail to bind IFN-gamma.

Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency.

Adolescent↗

PubMed1983

Characteristics of different cytoplasmic and nuclear estrogen receptors appearing with continuous hormonal exposure.

Biochemical properties of cytosol estrogen receptor (ERC) and nuclear estrogen receptor (ERN) from rat uteri continuously exposed in vivo to 17 beta-[2,4,6,7-3H] estradiol ( [3H]E2) for 6 h have been studied on the basis of immunological recognition and chromatographic elution patterns. Overall concentrations of ERC and ERN did not change during this time period when receptor-saturating concentrations of [3H]E2 were maintained (Jakesz, R., Kasid, A., and Lippman, M. E. (1983) J. Biol. Chem. 258, 11798-11806); however, biochemical characteristics were different in ERC and ERN after short or long term hormonal exposure. When ERC from rats treated with estradiol for 30 min was applied to HAP or DEAE columns, two different ER binding components were seen. DNA binding in a cell-free system revealed that these binding components represented an activated and a nonactivated ERC population. After long term hormonal exposure (6 h), only one component of ERC with low DNA binding could be shown despite the preservation of an equivalent quantity of cytoplasmic binding activity. This binder does not react with a monoclonal antibody directed against extranuclear estrogen receptor species. These data suggest disappearance of the activated ERC population, with appearance of a new, immunologically nonrecognizable ERC species with 6 h of continuous hormonal exposure. Elution profiles of ERN on HAP chromatography reveal 2 different binding components at 30 min and at 6 h of continuous [3H]E2 exposure. There is an increase of the population eluted at higher molarity after 6 h of in vivo treatment. This later eluting binding component is the major DNA binder in vitro. ERN from both time points are recognized immunologically by monoclonal antibody. After reaction with the antibody, the sedimentation coefficient shifted to 8-9 S on sucrose gradients, but the previously described faster sedimentation of ERN extracted 6 h after injection persisted. We conclude that ER in both cellular compartments undergoes time-dependent alterations, which may be involved in the initiation of hormone action.

Animals↗

PubMed2005

Expression patterns of chicken Toll-like receptor mRNA in tissues, immune cell subsets and cell lines.

The Toll-like receptor (TLR) family of cell surface molecules represent a major component of the pattern recognition system, which enables both vertebrates and invertebrates to detect invading microorganisms and mount an anti-microbial response. The TLR repertoire of mouse and man has been intensively studied and in this manuscript we report the identification of ESTs with homology to chTLR5 and chTLR7, and independently confirm the identification of chTLR 1/6/10 and 3 in the EST databases. We have determined the mRNA expression patterns for seven chicken TLRs (chTLR) in a wide range of chicken tissues, isolated immune cell types and cultured cells. Some of the chTLR were expressed in most tissues (chTLR1/6/10, chTLR3, chTLR4 and chTLR5), whereas others exhibited more restricted expression patterns (chTLR2 type 1, type 2 and chTLR7). Similarly distinct patterns of chTLR expression were seen with innate and adaptive immune cell types isolated from peripheral blood or spleen and with cultured cells of somatic or immunological origin. An understanding of the TLR repertoire for different tissues, immune cell subsets and cultured cell types allows more refined interpretation of immune induction in response to chicken pathogens.

Animals↗

PubMed1998

Effects of intraseptal infusions of N-methyl-D-aspartate receptor ligands on memory in an object recognition task in rats.

The present study describes the effects of intraseptal microinjections of N-methyl-D-aspartate (NMDA) or AP5, an agonist and an antagonist of the NMDA receptors, respectively, upon memory of rats. Animals were injected with the drug or vehicle immediately after the first exposure to two identical objects, and the duration of exploration of the familiar and a new object were evaluated 45 min or 24 h later. Vehicle-treated rats explored the new object longer than the familiar object when the intertrial time was 45 min, indicating that they remembered the familiar object, but not when the intertrial time was 24 h. The difference of exploration time between the objects was increased by NMDA, but not by AP5, when the intertrial time was 24 h, and decreased by AP5 when the intertrial interval was 45 min. These results suggest that NMDA and AP5 improves and disrupts, respectively, the consolidation in a working memory task.

2-Amino-5-phosphonovalerate↗

PubMed2004

[Recognition of virus infected cells by NK cells].

NK cells show cytotoxicity against virus-infected cells and tumor cells and play an important role in host defense. Although mecheanism of target cell recognition by NK cells have been unclear for a long time, it has recently been elucidated that certain NK cell receptors specifically recognize virus products. Furthermore, expression pattern of NK cell receptors, which consist of activating and inhibitory receptors, determines susceptibility to virus-infection. Here, we review recent progress of mechanism of recognition of virus-infected by NK cells.

Animals↗

PubMed2005

Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.

Natural killer T cells express a conserved, semi-invariant alphabeta T cell receptor that has specificity for self glycosphingolipids and microbial cell wall alpha-glycuronosylceramide antigens presented by CD1d molecules. Here we report the crystal structure of CD1d in complex with a short-chain synthetic variant of alpha-galactosylceramide at a resolution of 2.2 A. This structure elucidates the basis for the high specificity of these microbial ligands and explains the restriction of the alpha-linkage as a unique pathogen-specific pattern-recognition motif. Comparison of the binding of altered lipid ligands to CD1d and T cell receptors suggested that the differential T helper type 1-like and T helper type 2-like properties of natural killer T cells may originate largely from differences in their 'loading' in different cell types and hence in their tissue distribution in vivo.

Amino Acid Motifs↗

PubMed2005

Recognition patterns of HLA-A2-restricted human immunodeficiency virus-1-specific cytotoxic T-lymphocytes in a cohort of HIV-1-infected individuals.

The cytotoxic T-lymphocytes (CTL) response to three histocompatibility leukocyte antigen (HLA)-A2-restricted CTL epitopes was investigated in a cohort of 51 HLA-A2-positive human immunodeficiency-1 (HIV-1)-infected subjects. CTL activity was evaluated by testing peptide stimulated peripheral blood mononuclear cells (PBMC) in chromium release assays. The most prevalent CTL response was directed to the RT-peptide ILKEPVHGV (IV9) recognized by 37.3%. The p17-peptide SLYNTVATL (SL9), reported to be the immunodominant epitope in chronically infected untreated patients, was recognized only by 13.7%. Only 9.8% recognized both IV9 and SL9, and none recognized the RT-peptide VIYQYMDDL (VL9). CTL activity correlated significantly with absolute CD8 T-cell counts but not with CD4 counts, viral load, or antiviral therapy. Analysis of the recognition patterns of amino acid substitutions in the IV9 epitope revealed the presence of at least four functionally different T-cell receptors (TCR) in this cohort. All analyzed mutations within the TCR recognition site of this epitope could abrogate CTL recognition by individual CTL clones, but all were fully immunogenic for other CTL clones with peptide-sensitizing capacities similar to that of IV9. Further studies should be performed to evaluate whether a convergent epitope vaccination strategy using immunogenic variants of CTL epitopes is a feasible approach to broaden the TCR repertoire and to inhibit CTL escape.

Anti-HIV Agents↗

PubMed2004

[Significance of Toll-like receptors in the pathophysiology of surgical sepsis].

The discovery of Toll-like receptors has substantially changed our knowledge of pathogen recognition. 11 Toll-like receptors have so far been described in humans. These recognize distinct pathogen associated molecular patterns, as well as endogenous ligands and small molecular synthetic compounds. TLRs have a multifunctional role in pathogen-triggered immune responses and represent an important connection between the "innate" and "adaptive" immunity. The role of the TLRs in the recognition of pathogens renders them a key figure in the activation of the immune response during surgical sepsis. However, emerging evidence points to a fundamental role in tumorigenesis, transplantation, wound healing, atherogenesis and inflammatory bowel disease. The aim hence was to review experimental data pertaining to the activation of TLR signalling pathways in conditions associated with surgical sepsis. A systematic review of the literature was undertaken by searching the MEDLINE database for the period 1966-2004 without language restriction. The paper also analyses the possible therapeutic utilization of the TLR signalling pathways in surgical sepsis.

Humans↗

PubMed1995

T-cell epitopes of Phl p 1, major pollen allergen of timothy grass (Phleum pratense): evidence for crossreacting and non-crossreacting T-cell epitopes within grass group I allergens.

BACKGROUND: The use of peptides representing T-cell epitopes of allergens is a modern concept for improvement of specific immunotherapy. A prerequisite for this approach is the identification of T-cell epitopes of atopic allergens. METHODS: T-cell lines and 40 T-cell clones (TCC) specific for Phl p 1, the group I allergen of timothy grass (Phleum pratense), were established from the peripheral blood of nine patients allergic to grass pollen and mapped for epitope specificity by using overlapping dodecapeptides. Phenotype and cytokine production profile of TCC were investigated. Representative TCC were analyzed for HLA-restriction, T-cell receptor V beta gene usage, and crossreactivity with grass pollen extracts from Dactylis glomerata, Poa pratensis, Lolium perenne, Secale cereale, and selected amino acid sequence-derived peptides. RESULTS: Patients displayed IgE binding to all grass species investigated. Forty TCC were established. Fifteen T-cell epitopes could be identified on Phl p 1. Of 40 TCC, 39 displayed the helper cell (Th) phenotype; one clone was CD8+. Specific stimulation induced a Th2-like type of cytokine production in 20 of 39 TCC. Crossreactivity studies revealed crossreacting and non-crossreacting T-cell epitopes. CONCLUSION: Phl p 1, a major grass pollen allergen, harbors multiple T-cell epitopes. Species-specific and crossreacting T-cell epitopes exist among group I allergens of grasses. Epitope recognition patterns could not be correlated with particular HLA haplotypes. A restricted T-cell receptor V beta gene usage was not observed.

Allergens↗

PubMed2006

Plant cells recognize chitin fragments for defense signaling through a plasma membrane receptor.

Chitin is a major component of fungal cell walls and serves as a molecular pattern for the recognition of potential pathogens in the innate immune systems of both plants and animals. In plants, chitin oligosaccharides have been known to induce various defense responses in a wide range of plant cells including both monocots and dicots. To clarify the molecular machinery involved in the perception and transduction of chitin oligosaccharide elicitor, a high-affinity binding protein for this elicitor was isolated from the plasma membrane of suspension-cultured rice cells. Characterization of the purified protein, CEBiP, as well as the cloning of the corresponding gene revealed that CEBiP is actually a glycoprotein consisting of 328 amino acid residues and glycan chains. CEBiP was predicted to have a short membrane spanning domain at the C terminus. Knockdown of CEBiP gene by RNA interference resulted in the suppression of the elicitor-induced oxidative burst as well as the gene responses, showing that CEBiP plays a key role in the perception and transduction of chitin oligosaccharide elicitor in the rice cells. Structural analysis of CEBiP also indicated the presence of two LysM motifs in the extracellular portion of CEBiP. As the LysM motif has been known to exist in the putative Nod-factor receptor kinases involved in the symbiotic signaling between leguminous plants and rhizobial bacteria, the result indicates the involvement of partially homologous plasma membrane proteins both in defense and symbiotic signaling in plant cells.

Amino Acid Sequence↗

PubMed1978

Structure-activity study of beta-adrenergic agents using the SIMCA method of pattern recognition.

The SIMCA method of pattern recognition (PaRC) was used to analyze structure-activity data for a series of phenethylamine agonists and antagonists of the beta-adrenergic receptor. On the basis of physicochemical substituent parameters the SIMCA method classified correctly 100% of the agonists and 88% of the antagonists. In addition, parameters derived from the class models were correlated with the biological activities of the agonists and antagonists, respectively. Test compounds not included in the initial data analysis were classified and their activities estimated. The applicability of pattern recognition in structure-activity studies in general is discussed.

Adenylyl Cyclase Inhibitors↗