Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fc fragments of human immunoglobulin A(IgA) of IgA1 subclass and IgA2 subclass of A2m(1) allotype were prepared from IgA paraproteins by digestion with a protease from Clostridium sp. (M.O.-6). The N-terminal tetrapeptide of Val-Pro-Ser-Thr- for the Fc of IgA1 subclass, and that of Val-Pro-Pro-Pro- for the Fc of IgA2:A2m(1) allotype, were identified by sequence analysis. The site of cleavage by the protease was defined to be at the Pro-Val peptide bond, which is a common peptide bond present at 221-222 in both alpha chains. IgA of IgA2 subclass of A2m(2) allotype is resistant to the protease due to the different, Arg-Val, peptide bond at the same position.
Mol Immunol 1986 Feb
PMID:The site of cleavage in human alpha chains of IgA1 and IgA2:A2m(1) allotype paraproteins by the clostridial IGA protease. 308 49

Dimeric human secretory IgA was completely reduced with mercaptoethanol and alkylated with [14C]iodoacetamide. The component polypeptide chains were separated by high performance gel filtration in 5 M guanidine HCl into two fractions: one containing secretory component (SC) + heavy (H) chains; and the second containing light (L) + J chains. L and J chains were subsequently separated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS) or in alkaline urea. Calculations of the J chain stoichiometry in the dimeric secretory IgA (S-IgA) molecule were based on: the measurement of the ratio of radioactivities of SC + H chain and L + J chain-fractions or L chain- and J chain-fractions; the known stoichiometry of SC, H and L chains; and the known number of half-cystine residues in the component polypeptide chains of S-IgA molecule. The data demonstrated that one molecule of dimeric S-IgA contains approx. one J chain.
Mol Immunol 1986 May
PMID:The stoichiometry of J chain in human secretory dimeric IgA. 309 31

Immunoglobulins G, A, and M (IgG, IgA and IgM) were isolated from multiple sclerosis (MS) cerebrospinal fluid (CSF) and sera by Protein A-Sepharose (PAS) affinity chromatography or using solid-phase immunoabsorbents. An isoelectric point heterogeneous protein with apparent mol. wt of 74,000-80,000 was seen consistently when CSF Igs were immunoaffinity purified but was never seen when PAS was used for Ig purification. Control experiments exclude the binding of this protein non-specifically either to Sepharose or to Igs or to other CSF proteins. Analysis of purified Igs under non-reducing conditions leads to some reduction in staining pattern indicating that a portion of the protein may be disulfide linked to itself or to other CSF proteins. Immunoblot analysis of CSF Igs separated on 2-DE gels is consistent with a portion of the total CSF Ig protein existing as "free" heavy (H)-chains. PAS requires dimeric Fc fragment of Ig for binding; the differences in 2-DE gels of PAS and immunoaffinity purified Igs may be due to interaction of the 74,000-80,000 protein with "free" H-chain, which nevertheless, still leaves this complex available for binding by anti-H chain antisera. It has been previously suggested that the cytotoxicity of "free" H-chains is abrogated in the absence of the complementary L-chains by H-chain binding proteins; the protein reported here has features similar to these proteins reported previously and may be involved in some way in regulating Ig production in the MS central nervous system.
Mol Immunol 1986 Oct
PMID:Immunoglobulin heavy chain associated protein in multiple sclerosis cerebrospinal fluid. 309 76

Human gastric mucosa was removed at gastrectomy for duodenal ulcers. Intact mucosal layer and homogenized mucosal scrapings were incubated in vitro with L-[U-14C]leucine and with D-[U-14C]glucose and incorporation of radioactive label into IgA was investigated. 14C of both the precursors was incorporated into tissue IgA when intact gastric mucosa was incubated indicating synthesis of IgA by the tissue in vitro. IgA isolated from the media which bathed the luminal sides of the mucosae during incubation was also radioactive implying secretion of the newly-synthesized immunoglobulin into the media. When mucosal scrapings were incubated as homogenized suspensions, radioactivity of IgA was below the level of sensitivity of our methods. For analysis, IgA was separated from the bulk of radioactive mucosal proteins of the samples by isopycnic CsCl gradient centrifugation followed by gel filtration on Sephacryl S-200 or Sephadex G200 and then Sepharose 4B. The IgA-enriched Sepharose 4B fractions were subjected (1) to immunoprecipitation in agar gels by double diffusion against specific anti alpha-chain serum and (2) to SDS-polyacrylamide gel electrophoresis after reduction. Radioactivity of precipitated IgA, and of the protein band which corresponds to the alpha-chain of IgA on SDS-PAGE gels, was demonstrated autoradiographically. It is suggested that in vivo the mucosa is involved in local synthesis of the constituent IgA of gastric mucus.
Mol Immunol 1987 Jul
PMID:Synthesis of IgA by human gastric mucosa in vitro. 311 7

CNA/N mice bearing the X-linked immunodeficiency (xid) gene(s) demonstrate overall decreased numbers of B-cells, impaired immune responses to TI-2 antigens and decreased serum IgM, IgG3 and to a lesser extent IgG1 and IgA. In these experiments we examined equal number of B-cells (cells capable of regeneration of surface Ig) from PP, MLN and spleens of xid and control mice for immunoglobulin gene expression. B-cells present in CBA/N mice exhibit control levels of Ig isotype-specific mRNA accumulation and transcription. Oligonucleotide probes directed against membrane and secreted exons of mu, gamma and alpha genes were synthesized and hybridized to B-cell RNA from CBA/N and CBA/J mice to determine relative levels of each isotype- and exon-specific mRNA. Results revealed decreased alpha s RNA: alpha m RNA in splenic B-cells of xid mice when compared to control animals. Northern blot analysis of total tissue polysomal RNA demonstrated enhanced expression of the (larger) membrane form of alpha-mRNA (alpha m-RNA) of CBA/N when compared to CBA/J mice. This was especially apparent in splenic preparations; these and other studies have shown that both control and xid PP and MLN express enhanced levels of the membrane forms of each Ig heavy chain isotype RNA when compared to splenic RNA levels. These data suggest the presence of a defective regulation of membrane and secreted alpha in B-cell subpopulations of xid mice.
Mol Immunol 1987 Sep
PMID:Immunoglobulin gene expression in xid mice: defective expression of secreted and membrane alpha-heavy chain RNA. 311 16

Jackfruit lectin, jacalin, prepared from two batches of jackfruit seeds showed a different specificity in precipitating reaction in Agarose gel with various purified immunoglobulins and secretory components. Jacalin-P, extracted from jackfruit seeds from the Philippines, reacts only with serum IgA and secretory IgA of IgA1 subclass. Jacalin-O, extracted from jackfruit seeds from Okinawa prefecture in Japan, makes a strong precipitin are with IgA1 subclass and a weak precipitin arc with IgA2 subclass of IgA2m(2) allotype, IgM, IgD and IgE. Human secretory IgA of IgA1 subclass was isolated from human milk by a single jacalin-P affinity chromatography using D-galactose as a dissociating agent. From conventionally purified human secretory IgA preparation, secretory IgA of IgA1 subclass and of IgA2 subclass were separated from each other. The former was separated as jacalin-P adsorbed fraction and the latter as jacalin-P non-adsorbed fraction by the affinity chromatography. Subclass composition of secretory IgA in human milk was determined by the affinity column and was calculated to be 70% for IgA1 and 30% for IgA2 subclass. Jacalin affinity chromatography has several advantages compared with antibody coupled affinity chromatography, notably, high capacity, inexpensiveness, and very mild extraction of IgA1 subclass.
Mol Immunol 1987 Nov
PMID:A simple procedure for the isolation of human secretory IgA of IgA1 and IgA2 subclass by a jackfruit lectin, jacalin, affinity chromatography. 312 30

The control of production of the membrane (m) vs secreted (s) forms of immunoglobulin heavy chains was investigated in a panel of cell lines expressing different heavy chain classes but identical light chains (lambda) and variable regions. These cell lines could be induced towards Ig secretion by mitogen treatment. During this process a shift from m to s heavy chain production takes place. Here we show that, similarly to IgA- and IgE-producing B cells, in IgG2a-producing I.29 cells the gamma m-gamma s shift was accompanied by a shift in the corresponding mRNAs, with a decrease of gamma m mRNA and an increase of the gamma s mRNA in LPS-stimulated cells. By contrast, the micron mRNA was increased in LPS-stimulated IgM-producing cells, albeit these cells synthesized reduced amounts of micron polypeptides. The utilization of the translational level in the early steps of B lymphocyte maturation thus distinguishes the mode of regulation of mu chains from those of the other isotypes. In addition, in B cells a post-translational event blocks the secretion of IgM but not of IgG or IgE.
Mol Immunol 1988 Feb
PMID:The control of membrane and secreted heavy chain biosynthesis varies in different immunoglobulin isotypes produced by a monoclonal B cell lymphoma. 313 67

We report here a 54 base pair deletion in the CH3 exon of the alpha gene in the mouse myeloma W3129. This deletion results in a loss of 18 amino acids and a change from a glycine to a serine at position 464. The extent of the deletion was determined by sequencing a portion of CH3 cloned from a variant of W3129, and S1 nuclease protection showed the deletion pre-exists in the parental cell line. The deletion removes the donor splice site normally used in joining CH3 to the alpha membrane (MB) exon when forming MB-specific mRNA. Examination of cytoplasmic RNA by blot hybridization and S1 nuclease protection using MB-specific probes showed a complete lack of membrane mRNA in W3129 and its derivatives. An RNA transcript of unknown origin and function which includes sequences from the CH3-MB intron was seen in W3129 and in J558, an IgA, lambda myeloma with specificity for alpha (1----3) linked dextrans. We discuss the possible influence of the mutation on the W3129 protein. In contrast to the other myelomas studied in this laboratory, light chain loss variants are readily isolated from W3129 and are stable in their production of heavy chain [Dackowski and Morrison (1981) Proc. natn. Acad. Sci. U.S.A. 78, 7091-7095].
Mol Immunol 1988 May
PMID:The IgA myeloma W3129 contains a deletion in CH3 which prevents the formation of the membrane form of heavy chain mRNA. 313 59

We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.
J Mol Cell Immunol 1988
PMID:Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment. 315 Dec 47

Dinitrophenylated human serum albumin (DNP-HSA) with various DNP:HSA ratios was prepared by direct conjugation with dinitrobenzene sulfate or with a caproic acid spacer group (DNP-cap-HSA) using DNP-epsilon-amino-caproic acid N-hydroxy-succinimide ester. The substitution ratio and chemical linkage (presence of a spacer group) were shown to affect the degree of murine anti-DNP antibody binding to antigen, and hence the tissue deposition and efficiency of hepatobiliary transport. DNP-HSA (4.5:1), which poorly binds to IgA anti-DNP antibody, is inefficiently transported into mouse bile. In contrast, 9:1 DNP-cap-HSA readily forms complexes and is more effectively cleared by the hepatobiliary route. The IgA-mediated increase in liver deposition of DNP-cap-HSA (9:1) was found to be associated with an increase in antigen uptake by hepatocytes. In contrast, large complexes formed between DNP-HSA (49:1) and IgA anti-DNP antibody are taken up by nonparenchymal cells of the liver and thus are inefficiently transported into bile. These results suggest that the IgA-mediated uptake by phagocytic cells or hepatocytes of haptenated protein strongly depends on the degree of haptenation.
Mol Immunol 1988 Aug
PMID:IgA-mediated clearance and tissue deposition of dinitrophenylated human serum albumin at various DNP:HSA ratios. 318 69


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