Improving selection of αIIbβ3-binding phage antibodies with increased reactivity derived from immunized donors

Jacobin, Marie-Josée; Robert, Rémy; Pouns, Olivier; Laroche‐Traineau, Jeanny; Nurden, Alan T.; Peter, Karlheinz; Little, Melvyn; Clofent‐Sanchez, Gisèle

doi:10.1016/s1521-6616(03)00143-8

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…It is therefore not surprising that there are many positively charged amino acids (Arg, Lys, and His) in the CDRs of both heavy and light chains of our antibodies. Compared with other anti␣IIb␤3 antibodies, our antibodies do not contain RGD sequences; therefore, it is unlikely that our antibodies can cross-react with the RGD binding site of ␣IIb␤3 integrin (20). Although we have shown that the positively charged amino acids in the HCDR3 play a role in inducing platelet fragmentation, this result does not exclude the possible role(s) of other CDRs in heavy and light chains.…”

Section: Discussionmentioning

confidence: 84%

Platelet Fragmentation Requires a Specific Structural Conformation of Human Monoclonal Antibody against β3 Integrin

Nardi

et al. 2008

Journal of Biological Chemistry

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We have described an autoantibody against ␤3 (GPIIIa49 -66), a region of platelet integrin ␣IIb␤3 that is unique. It induces platelet fragmentation in the absence of complement via antibody activation of platelet NADPH oxidase and 12-lipoxygenase to release reactive oxygen species, which destroy platelets. To study the mechanism of anti-GPIIIa antibody-induced platelet fragmentation, we screened a human single chain Fv antibody library with the GPIIIa49 -66 peptide. Nine monoclonal antibodies were identified that were capable of binding to GPIIIa49 -66. Surprisingly, binding avidity for GPIIIa49 -66 did not correlate with activity of induction of platelet fragmentation. We therefore investigated the requirements for platelet fragmentation. Mutations were introduced into the heavy chain complementary-determining region-3 of clones 11, 43, and 54 by site-directed mutagenesis. The capability of these clones to induce platelet fragmentation or bind to GPIIIa49 -66 subsequently changed. Molecular modeling of these clones with their mutants revealed that the ability to induce platelet fragmentation is affected by the side chain orientation of positively charged amino acids in the heavy chain of residues 99 -102. Thus, a structural change in the conformation of antiGPIIIa49 -66 antibody contributes to its binding to the ␤3 integrin and subsequent antibody-induced platelet fragmentation and aggregate dissolution.

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Section: Discussionmentioning

confidence: 84%

Platelet Fragmentation Requires a Specific Structural Conformation of Human Monoclonal Antibody against β3 Integrin

Nardi

et al. 2008

Journal of Biological Chemistry

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“…Additionally, if the developed diagnostic agents were to reach the clinics, the use of humanlike antibodies should limit the risk of immunogenicity, saving the time that would be required for humanization of murine antibodies. HuAbs, 174 humanized, or human antibody fragments 124,152,157,162,177,189 therefore represent a class of ligands that will be theoretically safer to transfer to the clinics.…”

Section: Resultsmentioning

confidence: 99%

Recent Advances in the Molecular Imaging of Atherosclerosis

Larivière

Bonnet

Lorenzato

et al. 2020

Semin Thromb Hemost

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Atherosclerosis is the major underlying cause of cardiovascular diseases, the prevalence of which is continuously increasing, thus currently standing as the leading global cause of death. This pathology gradually develops over the course of 50 or more years throughout the life of an individual under the influence of a vast number of factors, both environmental and pathophysiological. This wealth of factors has elicited much research into molecular imaging, with purely diagnostic purposes or with the hope of engineering an efficient theranostic tool. To these ends, diverse nanomaterials with desirable, tunable properties have been explored by different teams, as described in this review.

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“…In our experience using the phage display technique, truncated or incomplete antibodies, usually overgrow the culture compared to the complete forms of antibodies. As a consequence, the phage antibodies recovered during biopanning are enriched in those incorrect truncated forms [29,30]. Fig.…”

Section: Isolation and Characterization Of Scfvmentioning

confidence: 98%

Isolation and characterization of a human antibody fragment specific for Ts1 toxin from Tityus serrulatus scorpion

Amaro¹,

Riaño-Umbarila²,

Becerril³

et al. 2011

Immunology Letters

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Improving selection of αIIbβ3-binding phage antibodies with increased reactivity derived from immunized donors

Cited by 6 publications

References 41 publications

Platelet Fragmentation Requires a Specific Structural Conformation of Human Monoclonal Antibody against β3 Integrin

Platelet Fragmentation Requires a Specific Structural Conformation of Human Monoclonal Antibody against β3 Integrin

Recent Advances in the Molecular Imaging of Atherosclerosis

Isolation and characterization of a human antibody fragment specific for Ts1 toxin from Tityus serrulatus scorpion

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