Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modification of protein Ag by proteolysis is one of the principal steps in the presentation of Ag to Th cells. However, little is known about the enzymes participating in these events, their specificity or the characteristics of the natural fragments that they produce. Cathepsin D (CD) is an aspartyl protease identified in endosomes of APC. In this report, the role of CD in the processing of OVA has been investigated. OVA digested in vitro with purified CD was able to stimulate IL-2 secretion by three different OVA-specific I-Ad restricted Th cell hybridomas when it was presented by fixed APC. The digest of OVA was recognized in the context of I-Ad, but not by I-Ak-restricted OVA-specific Th cells. No difference was observed in the ability of OVA digested with CD to stimulate Th cells in the absence of FCS or in the presence of protease inhibitors indicating that extracellular proteases were not likely to contribute to processing of OVA. Taken together, these results suggest that CD is necessary and sufficient for the generation of an antigenic epitope from OVA. A fragment containing the epitope was isolated from the OVA digest by reverse phase HPLC. This fragment, which migrates in SDS-PAGE as a 10-kDa polypeptide, is a potent epitope. Its capacity to activate Th cells is compared to that of the tryptic peptide OVA323-339.
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PMID:Role of cathepsin D in antigen presentation of ovalbumin. 132 88

Prothymosin alpha (ProT alpha) is an acidic polypeptide with potentiating effects on HLA-DR-restricted in vitro cellular immune response systems such as T cell proliferative responses to soluble proteins and cellular auto- or alloantigens. Experiments were performed to investigate the effect of ProT alpha on MHC class II Ag expression in human monocytes, murine splenocytes, and tumor cell lines at both protein and molecular levels. RIA and immunofluorescence analysis revealed that ProT alpha enhances HLA-DR surface Ag expression whereas Northern blot analysis demonstrated that ProT alpha causes significant accumulation of MHC class II mRNA. The enhancing effect of ProT alpha was demonstrated convincingly using precultured human peripheral monocytes, which are known to express decreased amounts of surface HLA-DR Ag, and HLA-DR-positive human cell lines. Moreover, ProT alpha was shown to induce HLA-DR Ag expression in a priori HLA-DR-negative tumor cells. Furthermore, ProT alpha was shown to be active in vivo. Splenocytes from mice pretreated with ProT alpha expressed more surface Ilpha Ag and contained more I alpha-specific mRNA. These findings suggest that ProT alpha may be important in the regulation of the immune response by enhancing MHC class II Ag expression in APC.
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PMID:Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. 154 15

The study was undertaken to clarify the role of atrial natriuretic polypeptide (ANP) in essential hypertension (EH). Plasma levels of alpha-human ANP (alpha hANP) were measured in 13 normal subjects, 25 patients with EH, 5 patients with primary aldosteronism (PA), 3 patients with renovascular hypertension (RVH) and 3 patients with pheochromocytoma (PC). Plasma level of alpha hANP (normal: 38.1 +/- 20.5pg/ml) was high in all hypertensive subjects. Synthetic alpha hANP was intravenously administrated to these subjects as follows: first a dose of 0.01 microgram/kg/min for 30 minutes, second a dose of 0.03 microgram/kg/min for 30 minutes, and then in normal subjects and EH 0.03 microgram/kg/min with a dose of 6.5 micrograms/kg/min of metoclopramide (MC) for 30 minutes. After the infusion of 0.01 microgram/kg/min alpha hANP, arterial blood pressure was significantly depressed in EH, RVH and PA, but not in PC. Marked diuretic and natriuretic responses were observed with increase in creatinine clearance and fractional sodium excretion in EH, RVH and PA, but not in PC. Sodium clearance/lithium clearance was slightly increased after infusion of 0.03 microgram/kg/min of alpha hANP in hypertensive subjects. Plasma renin activity did not change in low and normal renin EH and PA after infusion of either dose of alpha hANP, but was suppressed after 0.03 microgram/kg/min of alpha hANP in normal subjects and high renin EH, RVH and PC. Plasma aldosterone concentration was suppressed after either dose of alpha hANP in normal subjects and in EH, RVH and PC, but not in PA. Plasma cGMP concentration and urinary cGMP excretion were decreased after either dose of alpha hANP in both normal and hypertensive subjects. Furthermore, the decrease of PAC by alpha hANP was normalized by MC in normal subjects and EH. The rise in plasma cGMP by alpha hANP was suppressed by MC in both normal subjects and EH, but no changes were observed in arterial blood pressure and natriuretic response. These results suggest that alpha hANP secretion increases with elevation of blood pressure in EH, improving increase of circulatory blood volume, and alpha hANP may play a role in elevating blood pressure in EH. Moreover, it is considered that ANP increases sodium and water excretion through its effect on both renal glomeruli and distal tubules in EH. Hypotensive and natriuretic effects of ANP in EH may be concerned with dopaminergic activity which are probably related to the production of cGMP in the vascular wall and inhibition of the excretion of aldosterone in the adrenal cortex.
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PMID:[The significance of atrial natriuretic polypeptide in the cause of essential hypertension]. 165 13

A monoclonal antibody has been raised which recognizes an epitope, PAC 1 (postsynaptic density and cytoskeleton enriched), which is specifically associated with two novel glycoprotein components of forebrain postsynaptic density preparations and a novel neuronal cytoskeletal-associated polypeptide. The monoclonal antibody has been used to study the cellular and subcellular localization of these molecules and for the partial characterization of all three PAC 1 antigens in the rat. The PAC 1 epitope is present on two concanavalin A binding glycoproteins of apparent molecular weights 130,000 (pgp130) and 117,000 (pgp117). Both species are enriched in preparations of rat forebrain postsynaptic densities and to a lesser extent in synaptic membranes. The epitope is also expressed by a polypeptide of 155,000 mol. wt, cp155. This molecule is highly enriched in cytoskeleton rather than membrane preparations. Enzymic removal of N-linked carbohydrate lowers the molecular weights of the PAC 1 glycoproteins pgp130 and pgp117 by 11,000 and 14,000 respectively, and suggests that cp155 is not glycosylated. Detergent, alkaline and salt extractions of postsynaptic densities and synaptic membranes indicate that pgp130 and pgp117 are integral membrane glycoproteins and are tightly bound components of postsynaptic density preparations. Immunocytochemical studies of adult rat forebrain show prominent staining of pyramidal cell dendrites and perikarya. There is no evidence of glial staining. Electron microscope studies show staining of microtubules together with punctate deposits of plasma membrane-associated reaction product. Several criteria have been used to show that pgp130 and pgp117 do not correspond to other known neuronal glycoproteins of similar molecular weight. We conclude that the PAC 1 epitope is expressed by two novel synaptic glycoproteins which are very probably integral components of the postsynaptic density and by a novel neuronal cytoskeleton-associated protein.
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PMID:PAC 1: an epitope associated with two novel glycoprotein components of isolated postsynaptic densities and a novel cytoskeleton-associated polypeptide. 172 84

T cell binding to target cells involves not only the TCR and its MHC-bound ligand, but also a collection of additional proteins on both the T cell and its target. In an attempt to identify new molecules involved in this binding, mAb were raised against APC, and screened for their abilities to inhibit T cell recognition of Ag plus MHC on B cells. Six antibodies were identified that inhibited this reaction and that bound a cell-surface glycoprotein (Lgp55), with core polypeptide Mr 30,000 and a glycosylated Mr of approximately 55,000 depending upon the cell source. The properties of Lgp55 were consistent with it being the mouse homologue of a recently identified human ligand (intercellular adhesion molecule-2) for lymphocyte functional Ag-1 because the proteins are of comparable Mr, and antibody to Lgp55, like anti-lymphocyte functional antigen-1, blocks T cell recognition of Ag presented by B cells, but not of Ag presented by mouse fibroblasts.
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PMID:Identification of a new cell surface glycoprotein with accessory function in murine T cell responses. 213 99

PBMC from healthy adult individuals seropositive for measles virus (MV) were tested for their capacity to proliferate to UV-inactivated MV (UV-MV) or to autologous MV-infected EBV-transformed B cell lines (EBV-BC). MV-specific T cell responses were observed in 11 of 15 donors tested (stimulation index greater than 2), when optimal doses of UV-MV were used in proliferative assays. T cell clones were generated from PBMC of three donors responding to MV, by using either UV-MV or MV-infected autologous EBV-BC as APC. Stimulation with UV-MV generated exclusively CD3+ CD4+ CD8- MV-specific T cells, whereas after stimulation of PBMC with MV-infected EBV-BC, both CD3+ CD4+ CD8- and CD3+ CD4- CD8+ MV-specific T cell clones were obtained. Of 19 CD4+ T cell clones tested so far, 7 clones reacted specifically with purified fusion protein and 1 with purified hemagglutinin protein. Seven clones proliferated in response to the internal proteins of MV. Three clones reacted to whole virus but not to one of the purified proteins, whereas one clone seemed to recognize more than one polypeptide. Some of the T cell clones, generated from in vitro stimulation of PBMC with UV-MV, failed to recognize MV Ag when MV-infected EBV-BC were used as APC instead of UV-MV and PBMC. CD3+ CD4+ CD8- T cell clones recognized MV in association with HLA class II Ag (HLA-DQ or -DR), and most of them displayed CTL activity to autologous MV-infected EBV-BC. All CD4+ HLA class II-restricted CTL clones thus far tested were capable of assisting B lymphocytes for the production of MV-specific antibody. The CD4- CD8+ T cell clone MARO 1 recognized MV in association with HLA class I molecules and displayed cytotoxic activity toward MV-infected EBV-BC.
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PMID:Measles virus-specific human T cell clones. Characterization of specificity and function of CD4+ helper/cytotoxic and CD8+ cytotoxic T cell clones. 246 43

The contribution of viral infectivity to the expression of MHC class II-restricted T cell determinants was studied. A murine I-Ed-restricted T cell hybridoma recognizing the neuraminidase (NA) glycoprotein of influenza PR8 virus was stimulated strongly by infectious virus but failed to recognize antigen introduced on noninfectious virions. Recognition correlated with the de novo synthesis of viral NA within infected APC. The effectiveness of infectious virus did not depend strictly upon the amount of NA present in cultures, since high NA concentrations could be achieved by addition of nonreplicative virus without being stimulatory for NA-specific T cells. Recognition of a determinant generated only when synthesized in murine host cells was ruled out, since, in high concentration, NA isolated from purified egg-grown virions, even if reduced and alkylated, was recognized by the T hybridoma clone. Isolated NA was recognized when added to pre-fixed APC, suggesting that this form of antigen was able to bypass the usual processing pathway of exogenous proteins. Data suggest that endogenously synthesized antigen may contribute most significantly to presentation of labile T cell determinants. In addition to NA, recognition of an I-Ed-restricted determinant of the influenza hemagglutinin (HA) molecule, shown previously to have a relatively short half-life on APC surfaces, was enhanced greatly by infectious virus. In contrast, T cell recognition of a more stably expressed I-Ed-restricted site of the same HA polypeptide was only marginally improved on infected APC.
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PMID:Class II major histocompatibility complex-restricted T cells specific for a virion structural protein that do not recognize exogenous influenza virus. Evidence that presentation of labile T cell determinants is favored by endogenous antigen synthesis. 278 81

In order to examine the relationship between the renin-aldosterone system and atrial natriuretic polypeptide (ANP), we investigated the effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on the plasma concentrations of renin (PRC) and aldosterone (PAC), as well as the effects of captopril pretreatment on the natriuresis and blood pressure reduction induced by alpha-hANP in rats. Although alpha-hANP infused into conscious rats at 0.67 microgram min-1 kg-1 markedly increased the urinary excretion of sodium and decreased mean arterial pressure, its infusion did not change PRC; however, it significantly lowered PAC. Frusemide infusion at 20.8 micrograms min-1 kg-1 induced natriuresis comparable with that of alpha-hANP and it elevated both PRC and PAC, but mean arterial pressure was not altered. Pretreatment of rats with captopril did not have any significant influence on the acute natriuretic and hypotensive effects of alpha-hANP. Although the inhibitory effect of ANP on the renin-aldosterone system may be involved in the chronic modulation of body fluid volume and blood pressure, this effect does not seem to be directly involved in the acute natriuretic and hypotensive effects of the peptide.
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PMID:Relationship between the renin-aldosterone system and atrial natriuretic polypeptide in rats. 294 8

The effect of eight microbial protease inhibitors on Ag-presentation to six different Ag-specific T cell clones was investigated. We found that these protease inhibitors can inhibit Ag presentation in a highly selective manner. This selectivity was evident with T cell clones specific to different Ag as well as with T cells specific to the same Ag but differing in their H-2 restriction. The inhibition was to due to cytotoxicity or effects through the TCR because none of the eight inhibitors inhibited IL-2-induced T cell proliferation, and because they did not inhibit Ag presentation by fixed APC or synthetic polypeptide. The conclusion after these data suggests that each specific antigenic fragment is produced by a unique set of proteases.
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PMID:Selective inhibition of antigen presentation to cloned T cells by protease inhibitors. 326 20

The corecognition of antigen and class II major histocompatibility complex (MHC) molecules (Ia molecules) by the T-cell receptor is a cell surface event. Before antigen is recognized, it must be taken up, processed, and displayed on the surface of an Ia-bearing accessory cell (antigen-presenting cell, APC). The exact nature of antigen processing and the subsequent associations of antigen with the APC plasma membrane, Ia molecules, and/or the T-cell receptor are not well defined. To further analyze these events, we have characterized the processing and presentation of the soluble polypeptide antigen bovine insulin. We found that this antigen requires APC-dependent processing, as evidenced by the inability of metabolically inactivated APCs to present native antigen to antigen plus Ia-specific T-T hybridomas. The ability of the same APCs to present antigen after uptake and processing showed that this antigen subsequently becomes stably associated with the APC plasma membrane. To characterize the basis for this association, we analyzed its sensitivity to enzymatic digestion. APCs exposed to antigen, treated with phospholipase A2, and then immediately fixed lost the ability to stimulate bovine insulin plus I-Ad-specific hybridomas. In contrast, the ability of these same APCs to stimulate I-Ad allospecific hybridomas was unaffected. This effect of phospholipase is not mimicked by the broadly active protease Pronase, nor is there evidence for contaminating proteases in the phospholipase preparation. These results suggest that one consequence of antigen processing may be an antigen-lipid association that contributes to the anchoring of antigen to the APC membrane. The implications of this model are discussed.
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PMID:Phospholipase treatment of accessory cells that have been exposed to antigen selectively inhibits antigen-specific Ia-restricted, but not allospecific, stimulation of T lymphocytes. 352 95


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