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Dual specificity of anti-CXCL10-CXCL9 antibodies is governed by structural mimicry.
Fagète, Séverine; Rousseau, François; Magistrelli, Giovanni; Gueneau, Franck; Ravn, Ulla; Kosco-Vilbois, Marie H; Fischer, Nicolas.
Afiliación
  • Fagète S; NovImmune SA, 1228 Plan Les Ouates, Switzerland.
J Biol Chem ; 287(2): 1458-67, 2012 Jan 06.
Article en En | MEDLINE | ID: mdl-22041899
Dual-specific antibodies are characterized by an antigen-combining site mediating specific interactions with two different antigens. We have generated five dual-specific single chain variable fragments (scFv) that neutralize the activity of the two chemokines, CXCL9 and CXCL10, to bind to their receptor CXCR3. To better understand how these dual-specific scFvs bind these two chemokines that only share a 37% sequence identity, we mapped their epitopes on human CXCL9 and CXCL10 and identified serine 13 (Ser(13)) as a critical residue. It is conserved between the two chemokines but not in the third ligand for CXCR3, CXCL11. Furthermore, Ser(13) is exposed in the tetrameric structure of CXCL10, which is consistent with our finding that the scFvs are able to bind to CXCL9 and CXCL10 immobilized on glycosaminoglycans. Overall, the data indicate that these dual-specific scFvs bind to a conserved surface involved in CXCR3 receptor interaction for CXCL10 and CXCL9. Thus, structural mimicry between the two targets is likely to be responsible for the observed dual specificity of these antibody fragments.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Imitación Molecular / Quimiocina CXCL9 / Quimiocina CXCL10 / Anticuerpos de Cadena Única / Especificidad de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2012 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Imitación Molecular / Quimiocina CXCL9 / Quimiocina CXCL10 / Anticuerpos de Cadena Única / Especificidad de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2012 Tipo del documento: Article País de afiliación: Suiza