Differential regulation of glycosphingolipid biosynthesis in phenotypically distinct Burkitt's lymphoma cell lines

Taga, Samir; Mangeney, Marianne; Tursz, Thomas; Wiels, Joëlle

doi:10.1002/ijc.2910610220

Cited by 22 publications

(10 citation statements)

References 31 publications

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“…The Shiga toxin receptor, globotriaosylceramide (Gb3), is a neutral glycosphingolipid that was first identified as an Ag of Burkitt's lymphoma and other tumors (54,55). Some human epithelial and endothelial cells and a subset of B lymphocytes located in germinal centers express Gb3 (55)(56)(57), while most other cell types are Gb3 negative.…”

Section: Discussionmentioning

confidence: 99%

The B Subunit of Shiga Toxin Fused to a Tumor Antigen Elicits CTL and Targets Dendritic Cells to Allow MHC Class I-Restricted Presentation of Peptides Derived from Exogenous Antigens

Haicheur

Bismuth

Bosset

et al. 2000

The Journal of Immunology

121

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Immunization with peptide or recombinant proteins generally fails to elicit CTL, which are thought to play a key role in the control of virus-infected cells and tumor growth. In this study we show that the nontoxic B subunit of Shiga toxin fused to a tumor peptide derived from the mouse mastocytoma P815 can induce specific CTL in mice without the use of adjuvant. The Shiga B subunit acts as a vector rather than as an adjuvant, because coinjection of the tumor peptide and the B subunit as separate entities does not lead to CTL induction. We also demonstrated that in vitro the B subunit mediates the delivery of various exogenous CD8 T cell epitopes into the conventional MHC class I-restricted pathway, as this process is inhibited by brefeldin A and lactacystin and requires a functional TAP system. In contrast to other nonviral methods for transport of exogenous Ags into the endogenous MHC class I pathway that involve macropinocytosis or phagocytosis, the Shiga B subunit targets this pathway in a receptor-dependent manner, namely via binding to the glycolipid Gb3. Because this receptor is highly expressed on various dendritic cells, it should allow preferential targeting of the Shiga B subunit to these professional APCs. Therefore, the Shiga B subunit appears to represent an attractive vector for vaccine development due to its ability to target dendritic cells and to induce specific CTL without the need for adjuvant.

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Section: Discussionmentioning

confidence: 99%

The B Subunit of Shiga Toxin Fused to a Tumor Antigen Elicits CTL and Targets Dendritic Cells to Allow MHC Class I-Restricted Presentation of Peptides Derived from Exogenous Antigens

Haicheur

Bismuth

Bosset

et al. 2000

The Journal of Immunology

121

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“…Multiple tissue northern (MTN-H12) blot was obtained from CLONTECH. Eight human cell lines (Ramos, MutuI, BL2, Namalwa, Remb 1 , 8866, T51, and K562) were analyzed because P k synthase activity and antigen expression have been characterized previously (22,23). Total cellular RNA was extracted from cell lines using the RNeasy Midi kit (Qiagen SA).…”

Section: Methodsmentioning

confidence: 99%

“…However, North- Cloning of the P k ␣4-Galactosyltransferaseern analysis of various B cell lines (Fig. 6) shows that ␣4Gal-T1 expression clearly correlates with P k synthase activity and antigen expression in Burkitt's lymphoma cell lines (22,23).…”

Section: Fig 4 Expression Of Full Coding ␣4gal-t1 Variants In Highmentioning

confidence: 98%

Cloning and Expression of the Histo-blood Group PkUDP-galactose:Galβ1–4Glcβ1-Cer α1,4-Galactosyltransferase

Steffensen¹,

Carlier²,

Wiels³

et al. 2000

Journal of Biological Chemistry

115

137

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The molecular genetic basis of the P histo-blood group system has eluded characterization despite extensive studies of the biosynthesis of the P 1 , P, and P k glycolipids. The main controversy has been whether a single or two distinct UDP-Gal:Gal␤1-R 4-␣-galactosyltransferases catalyze the syntheses of the structurally related P 1 and P k antigens. The P 1 polymorphism is linked to 22q11.3-ter. Data base searches with the coding region of an ␣4GlcNAc-transferase identified a novel homologous gene at 22q13.2 designated ␣4Gal-T1. Expression of full coding constructs of ␣4Gal-T1 in insect cells revealed it encoded P k but not P 1 synthase activity. Northern analysis showed expression of the transcript correlating with P k synthase activity and antigen expression in human B cell lines. Transfection of P k -negative Namalwa cells with ␣4Gal-T1 resulted in strong P k expression. A single homozygous missense mutation, M183K, was found in six Swedish individuals of the rare p phenotype, confirming that ␣4Gal-T1 represented the P k gene. Sequence analysis of the coding region of ␣4Gal-T1 in P 1 ؉/؊ individuals did not reveal polymorphisms correlating with P 1 P 2 typing.The P histo-blood group system is the last of the known carbohydrate defined blood group systems for which the molecular genetic basis has not yet been clarified. The P blood group system involves two major blood group phenotypes, P 1 ϩ and P 1 Ϫ, with approximate frequencies of 80% and 20%, respectively (1, 2). P 1 Ϫ individuals normally express the P antigen (P 1 Ϫ is designated P 2 when P antigen expression is demonstrated), but the rare P k phenotype lacks the P antigen, while the rare p phenotype lack both P and P k antigens (for reviews, see Refs. 3-7). The P 1 ϩ phenotype is defined by expression of the neolacto-series glycosphingolipid P 1 (for structures, see Table I) (8). In contrast, the P, P k , and p antigens constitute intermediate steps in biosynthesis of globo-series glycolipids and give rise to P 1 k , P 2 k , and p phenotypes (9). Although the rare P k phenotype shows the same frequency of P 1 antigen expression as individuals expressing the P antigen, the p phenotype is always associated with lack of P 1 antigen expression. Extensive studies of the chemistry, biosynthesis, and genetics of the P blood group system identified the antigens as being exclusively found on glycolipids, with the blood group specificity being synthesized by at least two distinct glycosyltransferase activities; UDP-galactose:␤-D-galactosyl-␤1-R 4-␣-Dgalactosyltransferase (␣4Gal-T) 1 activity(ies) for P k and P 1 syntheses and UDP-GalNAc:Gb 3 3-␤-N-acetylgalactosaminyltransferase activity (EC 2.4.1.79) for P synthesis (for reviews, see Refs. 6 and 7). At least two independent gene loci, P and P 1 P k , are involved in defining these antigens. The P blood group-associated LKE antigen, shown to be the extended sialylated Gal-globoside structure (10), may involve polymorphism in an ␣2,3-sialyltransferase activity.A long-standing controversy has been whether a single...

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“…Although a number of genes coding for enzymes responsible for the synthesis of the carbohydrate moiety of glycosphingolipids have been recently isolated (3), no glycosyltransferase genes specific for the synthesis of globo series glycolipids have been isolated to date. Globotriaosylceramide (Gb3) is synthesized by ␣1,4-galactosyltransferase (␣1,4Gal-T) from LacCer (4). This glycolipid has been characterized on red blood cells as the P k antigen of the P blood group system (5).…”

mentioning

confidence: 99%

Molecular Cloning of Globotriaosylceramide/CD77 Synthase, a Glycosyltransferase That Initiates the Synthesis of Globo Series Glycosphingolipids

Kojima¹,

Fukumoto²,

Okajima³

et al. 2000

Journal of Biological Chemistry

129

120

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The expression cloning of a cDNA for globotriaosylceramide (Gb3)/CD77 synthase (␣1,4-galactosyltransferase) was achieved using an anti-Gb3 antibody and mouse L cells as a recipient cell line for the transfection. The isolated cDNA clone designated pVTR1 predicted a type II membrane protein with 19 amino acids of cytoplasmic domain, 26 amino acids of transmembrane region, and a catalytic domain with 308 amino acids. Introduction of the cDNA clone into L cells resulted in the neosynthesis of Gb3/CD77, and the extracts of the transfectant cells showed ␣1,4-galactosyltransferase activity only on lactosylceramide and galactosylceramide. In Northern blotting, a 2.3-kilobase mRNA was strongly expressed in heart, kidney, spleen, and placenta and weakly in colon, small intestine, and brain. Transfection of the cDNA into L cells resulted in the constitution of sensitivity to the apoptosis with Shiga-like toxins (verotoxins). Since Gb3/CD77 synthase initiates the synthesis of globo series glycolipids, the isolation of this cDNA will make possible further investigations into the function of its important series of glycolipids.

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Differential regulation of glycosphingolipid biosynthesis in phenotypically distinct Burkitt's lymphoma cell lines

Cited by 22 publications

References 31 publications

The B Subunit of Shiga Toxin Fused to a Tumor Antigen Elicits CTL and Targets Dendritic Cells to Allow MHC Class I-Restricted Presentation of Peptides Derived from Exogenous Antigens

The B Subunit of Shiga Toxin Fused to a Tumor Antigen Elicits CTL and Targets Dendritic Cells to Allow MHC Class I-Restricted Presentation of Peptides Derived from Exogenous Antigens

Cloning and Expression of the Histo-blood Group PkUDP-galactose:Galβ1–4Glcβ1-Cer α1,4-Galactosyltransferase

Molecular Cloning of Globotriaosylceramide/CD77 Synthase, a Glycosyltransferase That Initiates the Synthesis of Globo Series Glycosphingolipids

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