Disease relevance of Ighg

• It was shown recently that the IgG of patients with rheumatoid arthritis tends to lack the terminal galactose normally present on the conserved N-linked oligosaccharide situated on the CH2 domain [1].
• A number of systemic autoimmune diseases are associated with increased levels of the agalactosyl (G0) IgG isoforms that lack a terminal galactose from the CH2 domain oligosaccharide [2].
• CD4-PE40 is a recombinant toxin containing the binding domain of CD4 and a mutant form of Pseudomonas exotoxin A from which the cell binding domain has been removed [3].
• Glycosylated chimeric mouse-human anti-NIP IgG3 antibody produced by growth of the J558L mouse B cell plasmacytoma is characterised with respect to the single carbohydrate chain at Asn-297 in the CH2 domain indicating that the mouse cell glycosyl transferases dictate the pattern of glycosylation rather than the human CH region of the heavy chain [4].
• (2) Among the eight anti-IgA subclass antibodies, seven were directed against the CH2 domain of IgA whereas the anti-IgA1 1-155-1 recognised an epitope destroyed by Streptococcus sanguis IgA1 protease and localised in the hinge region of IgA1 [5].

Psychiatry related information on Ighg

• These studies suggest that the T15 idiotype is composed of at least six discrete overlapping Id whose locations range from the antigen binding region to the CH1 domain on TEPC15 [6].

High impact information on Ighg

• CH3 domain of IgG as binding site to Fc receptor on mouse lymphocytes [7].
• The introns separating the hinge from the CH2 domain and the CH2 from the CH3 domain are small (106 and 119 base pairs) [8].
• When compared with the parental gamma 2b heavy chain, M 311 was found to have a carboxyl terminal deletion comprising the CH3 domain [9].
• Certain of the mIgMRF that were weakly or not at all inhibitable by protein A were found to cross-react equally well with human Fc (CH2-CH3 domains) and pFc' (CH3 domain) fragments, indicating that the binding site for these monoclonals is at the CH3 domain [10].
• Two of hybridoma products expressing IdX identify CH3-domain determinants, and one has been assigned a CH2-domain specificity [11].

Biological context of Ighg

• These mice possess two CH2 IgH-1b and two CH2 Igh-1a/CH2 Igh-1d determinants, suggesting that these variant immunoglobulin arose from recombinations within the CH2 domain [12].
• The serum half-lives of a wild-type recombinant mouse monoclonal antibody of the IgG2b isotype and a mutant antibody differing from the wild-type antibody by a single amino acid substitution introduced into the CH2 domain, the replacement of Asn 297 by Ala to delete the conserved site of heavy chain glycosylation, were determined in the rat [13].
• The base sequence upstream from the junction, however, is unrelated to the amino acid sequence of the CH1 domain and the hinge region of all the gamma chains whose sequences have been determined [14].
• These findings suggest that, during their evolution, a double unequal crossing-over event has taken place at different intervening sequences, resulting in the transfer of the DNA segment coding for the CH1 domain or CH1-CH2 domains [15].
• Loss of a consensus splice signal in a mutant immunoglobulin gene eliminates the CH1 domain exon from the mRNA [16].

Anatomical context of Ighg

• The M3.11 cell line produces an Ig with a polypeptide deletion involving the CH3 domain [17].
• Gel analysis of specifically immunoprecipitated nascent chains indicates that the carbohydrate moiety can be added to the nascent heavy chains very soon after the presumptive asparaginyl glycosylation site (CH2 domain) is synthesized on the ribosome [18].
• For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region [19].
• An aglycosyl variant of this immunoglobulin, in which site-directed mutagenesis had been used to eliminate the carbohydrate attachment site in the CH2 domain by changing Asn297 to Ala, was compared in this system to aglycosyl immunoglobulin prepared from immunoglobulin-secreting cells treated with tunicamycin to inhibit N-linked glycosylation [20].
• The effect of synthetic peptides--corresponding to the amino acid sequences 289-301 (Y48) and 293-301 (Y91) within the CH-2 domain in the human IgG1 was studied on the oxazolone-specific primary and secondary antibody response isotype distribution and on the sheep erythrocyte (SRBC)-specific primary IgM response [21].

Associations of Ighg with chemical compounds

• Two fragments from IgG2a--one one from the CH2 domain, differing by only four amino acids from the homologous IgG2b fragment, and the other from the CH3 domain--specifically bound to the gamma 2a Fc receptor [22].
• The percentage of radioactivity glucosamine in the CH2 domain compared with the total Ig is about 25% instead of 75% as in the wild type [17].
• A proline-rich motif (PPLP) in the CH2 domain mediates this association [23].
• The remainder of the 47A constant region, including the hinge region, is identical to the 511 alpha chain, except for two conservative changes in the CH1 domain: serine-126 and theonine-197 in the 511 alpha chain are both replaced by alanine in the 47A chain [24].
• IgG is a glycoprotein with an N-linked carbohydrate structure attached to the CH2 domain of each of its heavy chains [25].

Physical interactions of Ighg

• Rather, binding of the fragment from the CH3 domain of IgG2a augmented the binding of the fragment from the CH2 domain of IgG2a but not that of the homologous fragment from IgG2b [22].
• The Fc gamma RI and Fc gamma RII binding sites have previously been mapped to the lower hinge and the adjacent surface of the CH2 domain although contributions of the CH2-CH3 interface to binding have been suggested [26].
• The COOH terminus of the IgG2 CH2 domain was found to contain accessory site(s) since it enhanced the binding properties of both IgG1 PLLGG and native IgG1 [27].
• A fimbrin-binding site was identified in the NH(2)-terminal domain of vimentin and the vimentin binding site at residues 143-188 in the CH1 domain of fimbrin [28].

Other interactions of Ighg

• One fragment from the CH2 domain of IgG2b bound to the gamma 2b Fc receptor [22].
• Our experiments demonstrate conclusively that the interaction of p53 and E1A with the CH3 domain resides exclusively in the TAZ2 domain, with no contribution from the ZZ domain [29].
• Oxygen-dependent hydroxylation of an asparagine residue has recently been reported to regulate C-TAD function by disrupting the interaction with the CH1 domain of the p300/CBP coactivator at normoxia [30].
• A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang) [31].
• These sites were shown to reside in the IgG2 CH2 domain, since the IgG1 CH2 module did not have enhanced activity in a panel of hybrid IgG1/IgG2 antibodies [27].

Analytical, diagnostic and therapeutic context of Ighg

• The synthetic peptide p23 representing residues 335 to 357 in the CH3 domain of human IgG1 was able to increase levels of secreted Ig in murine spleen cell cultures [32].
• To elucidate the biologic role of the dominant IgG subclass in the immune response to PS and to make an animal model of human IgG subclass deficiency, we generated mice with a targeted disruption of the exon encoding the CH1 domain of the gamma 3 heavy-chain constant region gene [33].
• The faster clearance rate, more rapid tumor targeting and lack of metabolic uptake in normal tissues demonstrated with the iodine-labeled CH2 domain-deleted cMAb may be an advantage for certain clinical protocols [34].

References