Characterization of a high-affinity human antibody with a disulfide bridge in the third complementarity-determining region of the heavy chain

2012 ◽  
Vol 25 (3) ◽  
pp. 125-135 ◽  
Author(s):  
Juan Carlos Almagro ◽  
Gopalan Raghunathan ◽  
Eric Beil ◽  
Dariusz J. Janecki ◽  
Qiang Chen ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Disulfide Bridge ◽  
Human Antibody ◽  
High Affinity ◽  
The Third ◽  
Complementarity Determining Region

scholarly journals Structure of the apo anti-influenza CH65 Fab

2015 ◽  
Vol 71 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Peter S. Lee ◽  
Ashley J. Arnell ◽  
Ian A. Wilson
Keyword(s):  
Neutralizing Antibodies ◽  
Affinity Maturation ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Human Antibody ◽  
Broadly Neutralizing Antibodies ◽  
High Affinity ◽  
Influenza Hemagglutinin ◽  
Universal Influenza Vaccine ◽  
Complementarity Determining Region

Influenza viruses remain a persistent challenge to human health owing to their inherent ability to evade the immune response by antigenic drift. However, the discovery of broadly neutralizing antibodies (bnAbs) against divergent viruses has sparked renewed interest in a universal influenza vaccine and novel therapeutic opportunities. Here, a crystal structure at 1.70 Å resolution is presented of the Fab of the human antibody CH65, which has broad neutralizing activity against a range of seasonal H1 isolates. Previous studies proposed that affinity maturation of this antibody lineage pre-organizes the complementarity-determining region (CDR) loops into an energetically favorable HA-bound conformation. Indeed, from the structural comparisons of free and HA-bound CH65 presented here, the CDR loops, and in particular the heavy-chain CDR3, adopt the same conformations in the free and bound forms. Thus, these findings support the notion that affinity maturation of the CH65 lineage favorably preconfigures the CDR loops for high-affinity binding to influenza hemagglutinin.

scholarly journals Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed Software Algorithm, JOINSOLVER

2004 ◽  
Vol 172 (11) ◽  
pp. 6790-6802 ◽  
Author(s):  
M. Margarida Souto-Carneiro ◽  
Nancy S. Longo ◽  
Daniel E. Russ ◽  
Hong-wei Sun ◽  
Peter E. Lipsky
Keyword(s):  
Heavy Chain ◽  
Antigen Binding ◽  
Ig Heavy Chain ◽  
Complementarity Determining Region

Characterization of a Mode of Specific Binding of Fibrin Monomer through its Amino-Terminal Domain by Macrophages and Macrophage Cell-Lines

1990 ◽  
Vol 63 (02) ◽  
pp. 193-203 ◽  
Author(s):  
John R Shainoff ◽  
Deborah J Stearns ◽  
Patricia M DiBello ◽  
Youko Hishikawa-Itoh
Keyword(s):  
Peritoneal Macrophages ◽  
Affinity Binding ◽  
Macrophage Cell ◽  
High Affinity Binding ◽  
Amino Terminal ◽  
High Affinity ◽  
Terminal Domain ◽  
Weak Binding ◽  
Amino Terminal Domain

SummaryThe studies reported here probe the existence of a receptor-mediated mode of fibrin-binding by macrophages that is associated with the chemical change underlying the fibrinogen-fibrin conversion (the release of fibrinopeptides from the amino-terminal domain) without depending on fibrin-aggregation. The question is pursued by 1) characterization of binding in relation to fibrinopeptide content of both the intact protein and the CNBr-fragment comprising the amino-terminal domain known as the NDSK of the protein, 2) tests of competition for binding sites, and 3) photo-affinity labeling of macrophage surface proteins. The binding of intact monomers of types lacking either fibrinopeptide A alone (α-fibrin) or both fibrinopeptides A and B (αβ-fibrin) by peritoneal macrophages is characterized as proceeding through both a fibrin-specific low density/high affinity (BMAX ≃ 200–800 molecules/cell, KD ≃ 10−12 M) interaction that is not duplicated with fibrinogen, and a non-specific high density/low affinity (BMAX ≥ 105 molecules/cell, KD ≥ 10−6 M) interaction equivalent to the weak binding of fibrinogen. Similar binding characteristics are displayed by monocyte/macrophage cell lines (J774A.1 and U937) as well as peritoneal macrophages towards the NDSK preparations of these proteins, except for a slightly weaker (KD ≃ 10−10 M) high-affinity binding. The high affinity binding of intact monomer is inhibitable by fibrin-NDSK, but not fibrinogen-NDSK. This binding appears principally dependent on release of fibrinopeptide-A, because a species of fibrin (β-fibrin) lacking fibrinopeptide-B alone undergoes only weak binding similar to that of fibrinogen. Synthetic Gly-Pro-Arg and Gly-His-Arg-Pro corresponding to the N-termini of to the α- and the β-chains of fibrin both inhibit the high affinity binding of the fibrin-NDSKs, and the cell-adhesion peptide Arg-Gly-Asp does not. Photoaffinity-labeling experiments indicate that polypeptides with elec-trophoretically estimated masses of 124 and 187 kDa are the principal membrane components associated with specifically bound fibrin-NDSK. The binding could not be up-regulated with either phorbol myristyl acetate, interferon gamma or ADP, but was abolished by EDTA and by lipopolysaccharide. Because of the low BMAX, it is suggested that the high-affinity mode of binding characterized here would be too limited to function by itself in scavenging much fibrin, but may act cooperatively with other, less limited modes of fibrin binding.

Gaunilo Parodies Anselm

2014 ◽  
Vol 17 (1) ◽  
pp. 45-71
Author(s):  
Geo Siegwart
Keyword(s):  
Detailed Comparison ◽  
The Third ◽  
Common Structure ◽  
Logical Reconstruction ◽  
Points Of View ◽  
And Function

The main objective is an interpretation of the island parody, in particular a logical reconstruction of the parodying argument that stays close to the text. The parodied reasoning is identified as the proof in the second chapter of the Proslogion, more specifically, this proof as it is represented by Gaunilo in the first chapter of his Liber pro insipiente. The second task is a detailed comparison between parodied and parodying argument as well as an account of their common structure. The third objective is a tentative characterization of the nature and function of parodies of arguments. It seems that parodying does not add new pertinent points of view to the usual criticism of an argument.

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