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Displaying record number 2062
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4 notes.
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8066: Isolation of human mAb, E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR has been reported. E10 showed binding to gp140 trimer and linear peptides derived from gp41 membrane proximal external region (MPER). IgG E10 use a famous V gene segment IGHV1-69 allelic variants including Fab 8066. Fine mapping of E10 epitope may potentiate MPER-based subunit vaccine development.
Yang2018
(ADCC)
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8066: Mini-Abs, monovalent and bivalent Fabs targeting the conserved internal trimeric coiled-coil of the Nheptad repeat (N-HR) of gp41 has been previously reported. Crystal structures and binding of closely related monovalent Fabs, Fab 8066 and Fab 8062 to covalently stabilized chimeric trimers of N-peptides of gp41,CCIZN36)3 has been reported. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 A° resolution, respectively. The structural data indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066.
Gustchina2013
(mimotopes, structure)
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8066: Crystal structure of the broadly neutralizing 8066 Fab in complex with 5-Helix was compared to the crystal structure of the non-neutralizing 8062 MAb and MAb D5. For all three Abs, binding affinity correlated with neutralization activity. Structural modeling analyses revealed relatively small differences in the interactions of this Ab with the antigen compared with 8062 and D5. CDR-H2 of 8062 was barely touching the surface of the 5-Helix, while CDR-H2 of 8066 was buried in the body of the bundle. Additional interactions, and higher affinity of shared interactions of 8066 compared to 8062 were found, indicating that the difference of 8062 and 8066 in their ability to bind 5-Helix reflects the difference in the neutralization activities of these two MAbs.
Gustchina2010
(antibody binding site, binding affinity, structure)
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Fab 8066: 8066 was derived by affinity maturation of the parent Fab 3674. 8066 bound to the same epitope as the parental Fab and showed improved binding affinity towards the target peptide compared to the parent Fab 3674. This was one of three maturated Abs that showed significant increases in both breadth and potency of neutralization against primary isolates of subtypes B and C, compared to the parental Fab. The improved neutralization activity was greater for the Fabs in monovalent than in bivalent formats.
Gustchina2009
(neutralization, binding affinity)
References
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4 references.
Gustchina2009
Elena Gustchina, John M. Louis, Christian Frisch, Francisco Ylera, Annette Lechner, Carole A. Bewley, and G. Marius Clore. Affinity Maturation by Targeted Diversification of the CDR-H2 Loop of a Monoclonal Fab Derived from a Synthetic Naive Human Antibody Library and Directed against the Internal Trimeric Coiled-Coil of gp41 Yields a Set of Fabs with Improved HIV-1 Neutralization Potency and Breadth. Virology, 393(1):112-119, 10 Oct 2009. PubMed ID: 19695655.
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Gustchina2010
Elena Gustchina, Mi Li, John M. Louis, D. Eric Anderson, John Lloyd, Christian Frisch, Carole A. Bewley, Alla Gustchina, Alexander Wlodawer, and G. Marius Clore. Structural Basis of HIV-1 Neutralization by Affinity Matured Fabs Directed against the Internal Trimeric Coiled-Coil of gp41. PLoS Pathog., 6(11):e1001182, 2010. PubMed ID: 21085615.
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Gustchina2013
Elena Gustchina, Mi Li, Rodolfo Ghirlando, Peter Schuck, John M. Louis, Jason Pierson, Prashant Rao, Sriram Subramaniam, Alla Gustchina, G. Marius Clore, and Alexander Wlodawer. Complexes of Neutralizing and Non-Neutralizing Affinity Matured Fabs with a Mimetic of the Internal Trimeric Coiled-Coil of HIV-1 gp41. PLoS One, 8(11):e78187, 2013. PubMed ID: 24244293.
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Yang2018
Zheng Yang, Xi Liu, Zehua Sun, Jingjing Li, Weiguo Tan, Weiye Yu, and Meiyun Zhang. Identification of a HIV gp41-Specific Human Monoclonal Antibody with Potent Antibody-Dependent Cellular Cytotoxicity. Front. Immunol., 9:2613, 2018. PubMed ID: 30519238.
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