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Query: UNIPROT:P06889 (Mol)
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This review summarizes recent data concerning the immunogenicity and immunomodulatory properties of glycosphingolipids. Many murine monoclonal antibodies that react with glycosphingolipids have been described recently. Most of these antibodies have been elicited by immunization with tumor cells and they may also bind to glycoproteins that contain similar carbohydrate sequences. Immunization with a variety of tissues, murine teratocarcinomas, myeloid leukemia, and carcinomas of the human lung, colon and stomach, has elicited antibodies that react with the sugar sequence Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal----. The suppression of lymphocyte responses to mitogens and antigens by gangliosides in vitro has led to suggestions that these glycolipids possess immunodulatory properties in vivo. The in vitro studies were performed by incubating mononuclear cells with either dispersions of pure gangliosides or ganglioside-containing liposomes. In vivo gangliosides are found only in cell membranes or in lipoproteins, where they represent a small mole percent of total lipids, and there is little information about the transfer of gangliosides from lipoproteins to cells in vivo. A role for gangliosides as modulators of the immune response is an interesting possibility that is not supported by physiologically relevant data at present.
Mol Immunol 1984 Nov
PMID:A review of the immunogenic and immuno-modulatory properties of glycosphingolipids. 639 57

The structural gene beta-Gal-1 encoding a beta-galactosidase (EC 3.2.1.23) of Drosophila melanogaster has been mapped by two independent genetic approaches. In the first, gene dosage dependent variation in beta-galactosidase activity levels in segmental aneuploids, generated from crosses of Y-autosome translocation stocks, was determined quantitatively. A dosage sensitive region on the left arm of chromosome 2 was identified and mapped to region 26A7-9. In the second approach, two null activity variants were isolated from wild populations. It was shown by deletion analysis that these nulls map to the same region as that determined by the segmental aneuploidy method. The results of an EMS mutagenesis screen showed that, besides the beta-Gal-1 locus, there are four loci defined by recessive lethal mutations which map in the 26A7-9 region.
Mol Gen Genet 1984
PMID:Cytogenic mapping and isolation of mutations of the beta-Gal-1 locus of Drosophila melanogaster. 644 Nov 4

Four different oligosaccharides were isolated from faeces collected from a blood group A, secretor, breast-fed infant. Three of these, GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4Glc (A-tetrasaccharide), GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4[Fuc alpha 1-3]Glc (A-pentasaccharide) and 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal beta 1-4Glc (A-heptasaccharide) have previously found in urine, whereas GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc (A-hexasaccharide) is a new compound. Structures were deduced by mass spectrometry of permethylated and N-trifluoroacetylated oligosaccharide alditols. The latter gave more structural information than the corresponding N-acetyl derivatives. The four oligosaccharides were tested for blood group A activity and all were found to inhibit the binding of anti-A antibody to blood group A substance.
Mol Immunol 1984 Nov
PMID:Blood group specific oligosaccharides from faeces of a blood group A breast-fed infant. 651 35

The relationship between erythrocyte autoreactive cold agglutinin (CA) antibodies and group carbohydrate-specific antibodies in hyperimmune rabbit Group C streptococcal antisera was investigated. The different antibody preparations examined were isolated from autologous erythrocyte, Group C carbohydrate, and alpha-GalNAc immunoabsorbents. Each population was subsequently tested for SRBC reactivity, RRBC autoreactivity, and carbohydrate and ligand reactivity, in hemagglutination assay, direct biphasic hemolytic and hemolytic inhibition assays, and radioimmunoassay. In absorption experiments, CA antibodies present in unfractionated serum and represented as purified IgG and IgM preparations, were reactive with Group C carbohydrate, but poorly reactive with alpha-GalNAc immunoabsorbent. In addition, CA antibody activity present in carbohydrate-eluted material, was absent in alpha-GalNAc-eluted material as determined by hemagglutination and direct hemolytic assay. By radioimmunoassay, carbohydrate-eluted and alpha-GalNAc-eluted streptococcal antibodies, and alpha-GalNAc-eluted BSA-alpha-GalNAc antibodies, exhibited similar reactivity with 125I-BSA-alpha-GalNAc antigen, and with GalNAc in radioimmunoassay inhibition experiments. In contrast to these results, both IgG and IgM CA antibodies exhibited a relatively low avidity toward 125I-BSA-alpha-GalNAc. Yet relative to the other antibody populations tested in radioimmunoassay inhibition experiments, CA antibodies did not exhibit a particularly significant difference in reactivity with GalNAc. However, recognition of other Gal-containing ligands, e.g. Mel and Lac, was restricted to the CA antibody preparations. These data suggest that CA antibodies present in Group C streptococcal antisera do not represent a higher affinity cross-reactive anticarbohydrate population, but instead perhaps represent cross-reactive carbohydrate-specific antibodies produced in response to nonimmunodominant Group C carbohydrate determinants.
Mol Immunol 1982 Mar
PMID:Properties of cold agglutinin and group carbohydrate-specific antibodies isolated from group C streptococcal antisera. 709 71

The binding of uropathogenic Escherichia coli to the globo series of glycolipids via P pili is a critical step in the infectious process that is mediated by a human-specific PapG adhesin. Three classes of PapG adhesins exist with different binding specificities to Gal alpha 4Gal-containing glycolipids. The structural basis for PapG recognition of the human glycolipid receptor globoside was investigated by using soluble saccharide analogues as inhibitors of bacterial haemagglutination. The minimum binding epitope was confirmed as the Gal alpha 4Gal moiety, but parts of the GalNAc beta and glucose residues, which flank the Gal alpha 4Gal in globoside (GbO4), were also shown to be important for strong binding. Furthermore, the same five hydroxyl groups of Gal alpha 4Gal in globotriasyl ceramide that were recognized by a previously characterized PapG variant were also recognized by the human-specific PapG in binding the GbO4 that dominates in the human kidney. Saccharide analogues that blocked haemagglutination also blocked the adherence of human uropathogenic E. coli to human kidney sections. Knowledge of the molecular details of the PapG-GbO4 interaction will make it possible to design antiadherence therapeutics.
Mol Microbiol 1995 Jun
PMID:Structural requirements for the glycolipid receptor of human uropathogenic Escherichia coli. 747 78

The structure of the N-linked sugar chains attached to three IgG antibodies, identical in amino acid sequence except for the changes required to introduce the carbohydrate addition sites, has been determined. All three antibodies are specific for dextran but differ in their ability to bind antigen. The heavy chains with a murine variable region (V region) attached to the human gamma 4 constant region were expressed in a murine hybridoma synthesizing the specific light chain. In addition to the glycosylation site in the Fc portion, each antibody has a different glycosylation site in the second complementarity determining region (CDR2) of the heavy chain (Asn54, Asn58, or Asn60). The sugar chains were released from purified Fab and Fc fragments by hydrazinolysis and converted to radioactive oligosaccharides by reduction with sodium borotritide. The structures of these radioactive oligosaccharides were determined by a combination of sequential exoglycosidase digestion and Bio-Gel P-4 and lectin column chromatography. For all three antibodies, the carbohydrate attached to the Fc portion was a mixture of complex-type biantennary sugar chains. The variable region carbohydrate structures attached at Asn54 and Asn58 were also complex-type but more highly sialylated than were the Fc-associated sugars. Moreover, unlike the Fc-associated sugars, a significant population of Fab-associated sugars contained a Gal alpha 1-->3 residue as a non-reducing terminus. In contrast, the carbohydrate attached at Asn60 was a high mannose structure. These results demonstrate that slight changes in the position of carbohydrate attachment within CDR2 of the variable region of the heavy chain can substantially alter carbohydrate processing and that complex-type carbohydrates contained within the same polypeptide chain can have different structures.
Mol Immunol 1995 Sep
PMID:Glycosylation of the variable region of immunoglobulin G--site specific maturation of the sugar chains. 747 98

Haemophilus influenzae lipopolysaccharide (LPS) contains structures, defined by monoclonal antibodies, which undergo phase variation. This investigation reports the nucleotide sequence of lic2A, which is required for the expression of at least three phase-variable LPS epitopes, one of which has the structure alpha Gal(1-4)beta Gal. lic2A contains multiple tandem repeats of the tetramer 5'-CAAT-3'. Previous studies have correlated changes in the number of 5'-CAAT-3' repeats with the phase-variable expression of the alpha Gal(1-4)beta Gal epitope. To obtain direct evidence for this, the 5'-CAAT-3' repeat region from lic2A was amplified directly from immunostained colonies and sequenced. This demonstrated that the variable expression of LPS epitopes, including alpha Gal(1-4)beta Gal, is in part directly dependent upon the number of copies of 5'-CAAT-3' within lic2A.
Mol Microbiol 1993 Sep
PMID:The role of a repetitive DNA motif (5'-CAAT-3') in the variable expression of the Haemophilus influenzae lipopolysaccharide epitope alpha Gal(1-4)beta Gal. 752 34

A method for the purification by affinity of antibodies of the IgM and IgG classes against the (Gal beta 1-->3 GalNAc-) epitope has been developed. The immunoadsorbent is based on the property of DEAE-Sephadex to bind acid glycolipids bearing this epitope, by electrostatic and hydrophobic interactions in a stable form in an aqueous medium. The acid glycolipid employed was asialo-GM1 ganglioside (GA1) derivatized to produce a carboxyl function on the olefinic bond of the sphingosine moiety (GA1 acid). The DEAE-Sephadex-GA1 acid complex was used to purify the antibodies of the IgG class from serum of an immunized rabbit and of the IgM class from a human serum. The specific activities of the purified antibodies were 1,200- to 2,400-fold higher, and the antibody activities were quantitatively recovered respect to the untreated sera, in both cases. The sequential use of two immunoadsorbents: DEAE-Sephadex-ganglioside and DEAE-Sephadex-GA1 acid, allows the separation of the two classes of immunoglobulins that recognize the same sugar residues in glycolipids.
Biochem Mol Biol Int 1994 May
PMID:Glycolipids noncovalently bound to DEAE-Sephadex. Use of the complexes for purification of IgM and IgG anti-(Gal beta 1-->3 GalNAc-) antibodies. 752 99

Human galanin (hGal) is an important neuro-modulator present in the brain, gastrointestinal system and the hypothalamo-pituitary axis. A specific receptor for hGal has been identified in various areas in human brain. A single class of high affinity binding sites was found on plasma membranes of the amygdala (Kd 0.23 nM, Bmax 44 fmol/mg), the hypothalamus (Kd 0.20 nM, Bmax 25 fmol/mg) and the cortex cerebri (Kd 0.11 nM, Bmax 8.2 fmol/mg). Other brain areas, i.e. cerebellum, thalamus or pons, expressed binding sites of identical high affinity in lower quantities (Bmax < 3 fmol/mg). Specific binding of 125I-labelled hGal was found to be reversible, time- and temperature-dependent and inhibited by Ca2+, Na+ and K+ ions at a concentration of 5 mM. Non-hydrolysable guanosine nucleotides potently reduced specific binding of 125-I-labelled hGal by more than 80%. Synthetic hGal analogues substituted in the N-terminal region exhibited strongly reduced binding affinity for the hGal receptor. Using 3-[(3-cholamidopropyl) dimethylammonio]-2-hydroxy-1-propanesulphonate, hGal receptors were successfully solubilized from human cortical membranes, exhibiting no significant loss of binding affinity. Affinity cross-linking to 125I-labelled hGal revealed a labelled band of approximately 60 kDa sensitive to unlabelled Gal. This putative hGal receptor is glycosylated since its molecular size was reduced after treatment with endoglycosidase F. Receptors bound to 125I-labelled hGal could be specifically adsorbed to wheat germ agglutinin and ricinus communis agglutinin, suggesting that receptor glycosylation involves N-acetyl glucosamine and galactose respectively.
J Mol Endocrinol 1994 Dec
PMID:Identification and biochemical characterization of the human brain galanin receptor. 753 60

Three components involved in catabolite repression (CR) of gene expression in Bacillus have been identified. The cis-acting catabolite responsive element (CRE), which is present in many genes encoding carbon catabolic enzymes in various species of the Gram-positive bacteria, mediates CR of several genes in Bacillus subtilis, Bacillus megaterium, and Staphylococcus xylosus. CR of most genes regulated via CRE is also affected by the trans-acting factors CcpA and HPr. Similarities between CcpA and Lac and Gal repressors suggest binding of CcpA to CRE. HPr, a component of the phosphoenolpyruvate:sugar phosphotransferase system, undergoes regulatory phosphorylation at a serine residue by a fructose-1,6-diphosphate-activated kinase. A mutant of HPr, which is not phosphorylatable at this position because of an exchange of serine to alanine, lacks CR of several catabolic activities. This mutant phenotype is similar to the one exhibited by a ccpA mutant. Direct protein-protein interaction between CcpA and HPr(Ser-P) was recently demonstrated and constitutes a link between metabolic activity and CR.
Mol Microbiol 1995 Feb
PMID:Catabolite repression in Bacillus subtilis: a global regulatory mechanism for the gram-positive bacteria? 754 Feb 44


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