Interactions between Fab and Fc regions in liganded immunoglobulin G

Romans, D. G.; Tilley, C A; Dorrington, Keith J.

doi:10.1016/0161-5890(79)90085-3

Cited by 15 publications

(7 citation statements)

References 84 publications

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“…On the other hand, the termini of I structures such as Fuc␣1-2Gal␤1-4GlcNAc(Fuc␣1-2Gal␤1-4GlcNAc␤1-6)Gal (33,34) provide the H antigen or its modifications, the A and B antigens, on two neighboring N-acetyllactosamines. Such bivalent antigenic structures function as much better ligands for anti-ABO antibodies than single antigenic structures (38). In the same vein, it has been demonstrated that multivalent sialyl Lex polylactosamines at very low concentrations can inhibit L-selectin-mediated lymphocyte binding to the endothelium of lymph nodes (39) and rejecting organ transplants (21, 40 -42).…”

Section: Discussionmentioning

confidence: 93%

The Centrally Acting β1,6N-Acetylglucosaminyltransferase (GlcNAc to Gal)

Mattila¹,

Salminen²,

Hirvas³

et al. 1998

Journal of Biological Chemistry

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In the present experiments the cDNA coding for a truncated form of the ␤1,6N-acetylglucosaminyltransferase responsible for the conversion of linear to branched polylactosamines in human PA1 cells was expressed in Sf9 insect cells. The catalytic ectodomain of the enzyme was fused to glutathione S-transferase, allowing effective one-step purification of the glycosylated 67-74-kDa fusion protein. Typically a yield of 750 g of the purified protein/liter of suspension culture was obtained. The purified recombinant protein catalyzed the transfer of GlcNAc from UDP-GlcNAc to the linear tetrasaccharide Gal␤1-4GlcNAc␤1-3Gal␤1-4-GlcNAc, converting the acceptor to the branched pentasaccharide Gal␤1-4GlcNAc␤1-3(GlcNAc␤1-6)Gal␤1-4-GlcNAc as shown by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry, degradative experiments, and 1 H NMR spectroscopy of the product. By contrast, the recombinant enzyme did not catalyze any reaction when incubated with UDP-GlcNAc and the trisaccharide GlcNAc␤1-3Gal␤1-4GlcNAc. Accordingly, we call the recombinant ␤1,6-GlcNAc transferase cIGnT6 to emphasize its action at central rather than peridistal galactose residues of linear polylactosamines in the biosynthesis of blood group I antigens. Taken together this in vitro expression of I-branching enzyme, in combination with the previously cloned enzymes, ␤1,4galactosyltransferase and ␤1,3N-acetylglucosaminyltransferase, should allow the general synthesis of polylactosamines based totally on the use of recombinant enzymes.

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Section: Discussionmentioning

confidence: 93%

The Centrally Acting β1,6N-Acetylglucosaminyltransferase (GlcNAc to Gal)

Mattila¹,

Salminen²,

Hirvas³

et al. 1998

Journal of Biological Chemistry

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“…It has been demonstrated that multivalent sialyl Le x poly-N-acetyllactosamines inhibit L-selectin-mediated binding and the rejection of organ transplants with much better efficacy than monovalent sialyl Le x poly-N-acetyllactosamines (23,24). Similarly, blood group H antigens present at both termini in branched poly-N-acetyllactosamines were shown to have much better avidity to anti-ABO antibodies than linear poly-N-acetyllactosamines containing single antigenic structures (25). It was suggested that expression of i antigen in fetal erythrocytes minimizes a detrimental immune response when mother and fetus have incompatible blood group antigens (25).…”

mentioning

confidence: 99%

“…Similarly, blood group H antigens present at both termini in branched poly-N-acetyllactosamines were shown to have much better avidity to anti-ABO antibodies than linear poly-N-acetyllactosamines containing single antigenic structures (25). It was suggested that expression of i antigen in fetal erythrocytes minimizes a detrimental immune response when mother and fetus have incompatible blood group antigens (25).…”

mentioning

confidence: 99%

Regulation of I-Branched Poly-N-Acetyllactosamine Synthesis

Ujita

McAuliffe

Suzuki

et al. 1999

Journal of Biological Chemistry

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I-branched poly-N-acetyllactosamine is a unique carbohydrate composed of N-acetyllactosamine branches attached to linear poly-N-acetyllactosamine, which is synthesized by I-branching ␤1,6-N-acetylglucosaminyltransferase. I-branched poly-N-acetyllactosamine can carry bivalent functional oligosaccharides such as sialyl Lewis x , which provide much better carbohydrate ligands than monovalent functional oligosaccharides. In the present study, we first demonstrate that I-branching ␤1,6-N-acetylglucosaminyltransferase cloned from human PA-1 embryonic carcinoma cells transfers ␤1,6-linked GlcNAc preferentially to galactosyl residues of N-acetyllactosamine close to nonreducing terminals. We then demonstrate that among various ␤1,4-galactosyltransferases (␤4Gal-Ts), ␤4Gal-TI is most efficient in adding a galactose to linear and branched poly-Nacetyllactosamines. When a ␤1,6-GlcNAc branched poly-N-acetyllactosamine was incubated with a mixture of ␤4Gal-TI and i-extension ␤1,3-N-acetylglucosaminyltransferase, the major product was the oligosaccharide with one N-acetyllactosamine extension on the linear Gal␤134GlcNAc␤133 side chain. Only a minor product contained galactosylated I-branch without N-acetyllactosamine extension. This finding was explained by the fact that ␤4Gal-TI adds a galactose poorly to ␤1,6-GlcNAc attached to linear poly-N-acetyllactosamines, while ␤1,3-N-acetylglucosaminyltransferase and ␤4Gal-TI efficiently add N-acetyllactosamine to linear poly-Nacetyllactosamines. Together, these results strongly suggest that galactosylation of I-branch is a rate-limiting step in I-branched poly-N-acetyllactosamine synthesis, allowing poly-N-acetyllactosamine extension mostly along the linear poly-N-acetyllactosamine side chain. These findings are entirely consistent with previous findings that poly-N-acetyllactosamines in human erythrocytes, PA-1 embryonic carcinoma cells, and rabbit erythrocytes contain multiple, short I-branches.

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“…Segmental motion within the IgG molecule, which permits the Fab regions to assume a variety of orientations in space relative to the Fc region, is mediated by the hinge (3). Segmental flexibility, which allows variation in the distance between the antibody-combining sites located at the distal ends of the Fab regions, serves the important function of allowing bivalent attachment of antibodies to antigenic determinants even if the latter form a fixed array (for example, on a cell surface) (4). Finally, the hinge region serves as a "spacer," thus minimizing the population of conformational states in which close association between the Fab and Fc regions is achieved.…”

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confidence: 99%

Expression of biological effector functions by immunoglobulin G molecules lacking the hinge region.

Klein¹,

Haeffner‐Cavaillon²,

Isenman³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Several biological effector functions mediated by sites on the Fc region of human IgG1 have been studied in two variant IgGlK monoclonal proteins (Dob and Lec) which contain deletions corresponding to the entire hinge region of the heavy chains. Neither Dob nor Lec protein in aggregated form was able to activate the classical complement pathway, and this was shown to be due to an inability to bind the first component of complement (Cl). By rosette inhibition assays, Dob and Lec proteins were shown to have no measurable affinity for Fc receptors on human B cells or neutrophils. Dob and Lec proteins had a much reduced affinity for Fc receptors on the murine macrophage-like cell line P388D1 when compared to normal human IgGi. Furthermore, the hinge-deleted proteins were able to compete with murine IgG2b for P388D, receptors but not with murine IgG2a. In contrast, the binding of Dob and Lec proteins to protein A from Staphylococcus aureus was entirely normal. The functional consequences of the hinge deletion were parallel to those seen when normal IgGI was reduced and alkylated. It was concluded that the functional impotency of Dob and Lec proteins was related to the close association between the Fab and Fc regions in these molecules and the limited degree of segmental flexibility permitted in the absence of the hinge region. The data also suggest a major role for the C'y2 domain (C is the constant region) in mediating effector functions in normal IgGl.

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Interactions between Fab and Fc regions in liganded immunoglobulin G

Cited by 15 publications

References 84 publications

The Centrally Acting β1,6N-Acetylglucosaminyltransferase (GlcNAc to Gal)

The Centrally Acting β1,6N-Acetylglucosaminyltransferase (GlcNAc to Gal)

Regulation of I-Branched Poly-N-Acetyllactosamine Synthesis

Expression of biological effector functions by immunoglobulin G molecules lacking the hinge region.

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