Modeling study of antibody combining sites to (alpha 1-6)dextrans. Predictions of the conformational contribution of VL-CDR3 and J kappa segments to groove-type combining sites.

Wang, Guoyin; Hubbard, J. M.; Kabat, Elvin A.

doi:10.1016/s0021-9258(20)80765-0

Cited by 10 publications

(2 citation statements)

References 30 publications

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“…Prof. Kabat and colleagues noted that ''These studies demonstrated that the upper limit for the size of an anti-(a1-6)dextran combining site was complementary to six or seven (a1-6)-linked glucoses in dextran, and the lower limit was complementary between one to two such (a1-6)-linked glucoses'' 91 [quoted from ref. 92]. These discoveries fit well with studies on blood group antigens in glycolipids, where specific antibodies have been identified that recognize large complex determinants (see Fig.…”

Section: Sizes Of Glycan Determinantssupporting

confidence: 70%

The repertoire of glycan determinants in the human glycome

2009

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The number of glycan determinants that comprise the human glycome is not known. This uncertainty arises from limited knowledge of the total number of distinct glycans and glycan structures in the human glycome, as well as limited information about the glycan determinants recognized by glycan-binding proteins (GBPs), which include lectins, receptors, toxins, microbial adhesins, antibodies, and enzymes. Available evidence indicates that GBP binding sites may accommodate glycan determinants made up of 2 to 6 linear monosaccharides, together with their potential side chains containing other sugars and modifications, such as sulfation, phosphorylation, and acetylation. Glycosaminoglycans, including heparin and heparan sulfate, comprise repeating disaccharide motifs, where a linear sequence of 5 to 6 monosaccharides may be required for recognition. Based on our current knowledge of the composition of the glycome and the size of GBP binding sites, glycoproteins and glycolipids may contain approximately 3000 glycan determinants with an additional approximately 4000 theoretical pentasaccharide sequences in glycosaminoglycans. These numbers provide an achievable target for new chemical and/or enzymatic syntheses, and raise new challenges for defining the total glycome and the determinants recognized by GBPs.

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Section: Sizes Of Glycan Determinantssupporting

confidence: 70%

The repertoire of glycan determinants in the human glycome

2009

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“…Variable light CDR3 length reportedly influences the loop configuration of the antibody/antigen-binding site. In fact, Wang et al has suggested that a change in length of the VL CDR3 may have a more significant effect than amino acid substitutions [42]. These findings suggest that the homogeneous VL CDR3 length may be a feature of polyreactive antibodies while PPS-specific antibodies do not have this restriction.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of human polyreactive pneumococcal polysaccharide antibodies

Thompson¹,

Khaskhely²,

Malhotra³

et al. 2012

OJI

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Natural antibodies serve as the body’s first line of defense against pneumococcal challenge. Polyreactive human pneumococcal polysaccharide IgG antibodies have not been extensively studied. We analyzed human polyreactive antibodies that bind multiple pneumococcal polysaccharides, including PPS14 and PPS23F. These antibodies were isolated from single pneumococcal polysaccharide specific B cells allowing for the analysis of human immunoglobulins with natively paired variable regions. Although isolated individually, these antibodies demonstrated similar characteristics. Most antibodies possessed a variable light chain with a CDR3 length made up of nine amino acids and relatively high number of flexible amino acids in combined VH/VL. While these antibodies were polyreactive and structurally alike, kinetic analysis revealed unique K<sub>D</sub> values. Variable chains are responsible for antigen recognition whereas antibody fine specificity is affected by isotype structure. To investigate the contribution of the constant region of these isotypes and their effect on antibody avidity to pneumococcal polysaccharide, the polyreactive variable regions were expressed as IgG1 or IgG2 and subjected to kinetic analysis. The IgG1 antibodies uniformly had a stronger avidity to PPS14 and PPS23F compared to IgG2. To further document the importance of the constant region in antibody avidity and fine specificity, analysis of antibody F(ab)’2 fragment binding to PPS14 and PPS23F resulted in similar K<sub>D</sub> values. These studies suggest that antigen recognition by polyreactive antibodies is determined by a conserved variable light chain CDR3 length and longer, more flexible variable heavy CDR3s when compared to pneumococcal polysaccha-ride-specific sequences while differences in specific avidities are modulated by antibody isotype

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Correlation of antigenic epitope and antibody gene usage in the human immune response to Streptococcus pneumoniae type 23F capsular polysaccharide

Reason¹,

Zhou²

2004

Clinical Immunology

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Modeling study of antibody combining sites to (alpha 1-6)dextrans. Predictions of the conformational contribution of VL-CDR3 and J kappa segments to groove-type combining sites.

Cited by 10 publications

References 30 publications

The repertoire of glycan determinants in the human glycome

The repertoire of glycan determinants in the human glycome

Isolation and characterization of human polyreactive pneumococcal polysaccharide antibodies

Correlation of antigenic epitope and antibody gene usage in the human immune response to Streptococcus pneumoniae type 23F capsular polysaccharide

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