Paratope plasticity in diverse modes facilitates molecular mimicry in antibody response

Krishnan, Lavanya ; Lomash, Suvendu ; Jeevan Raj, Beena Patricia ; Kaur, Kanwal J. ; Salunke, Dinakar M. (2007) Paratope plasticity in diverse modes facilitates molecular mimicry in antibody response The Journal of Immunology, 178 (12). 7923 -7931. ISSN 0022-1767

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The immune response against methyl-α -D-mannopyranoside mimicking 12-mer peptide (DVFYPYPYASGS) was analyzed at the molecular level towards understanding the equivalence of these otherwise disparate Ags. The Ab 7C4 recognized the immunizing peptide and its mimicking carbohydrate Ag with comparable affinities. Thermodynamic analyses of the binding interactions of both molecules suggested that the mAb 7C4 paratope lacks substantial conformational flexibility, an obvious possibility for facilitating binding to chemically dissimilar Ags. Favorable changes in entropy during binding indicated the importance of hydrophobic interactions in recognition of the mimicking carbohydrate Ag. Indeed, the topology of the Ag-combining site was dominated by a cluster of aromatic residues, contributed primarily by the specificity defining CDR H3. Epitope-mapping analysis demonstrated the critical role of three aromatic residues of the 12-mer in binding to the Ab. Our studies delineate a mechanism by which mimicry is manifested in the absence of either structural similarity of the epitopes or conformational flexibility in the paratope. An alternate mode of recognition of dissimilar yet mimicking Ags by the anti-peptide Ab involves plasticity associated with aromatic/hydrophobic and van der Waals interactions. Thus, antigenic mimicry may be a consequence of paratope-specific modulations rather than being dependent only on the properties of the epitope. Such modulations may have evolved toward minimizing the consequences of antigenic variation by invading pathogens.

Item Type:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:52490
Deposited On:04 Aug 2011 08:04
Last Modified:18 May 2016 06:01

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