Plasticity within the antigen-combining site may manifest as molecular mimicry in the humoral immune response

Goel, Manisha ; Krishnan, Lavanya ; Kaur, Surinder ; Kaur, Kanwal J. ; Salunke, Dinakar M. (2004) Plasticity within the antigen-combining site may manifest as molecular mimicry in the humoral immune response The Journal of Immunology, 173 (12). pp. 7358-7367. ISSN 0022-1767

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Official URL: http://www.jimmunol.org/content/173/12/7358.short

Abstract

Structural and physiological facets of carbohydrate-peptide mimicry were addressed by analyzing the Ab response to a-D-mannopyranoside. mAbs against a-D-mannopyranoside were generated and screened with the carbohydrate-mimicking 12 mer (DVFYPYPYASGS) peptide. Three mAbs, 2D10, 1H11, and 1H7, which were subjected to detailed analysis, exhibit diverse V gene usage, indicating their independent germline origins. Although the mAb 1H7 was specific in binding only to the immunizing Ag, the Abs 2D10 and 1H11 recognize the 12 mer peptide as well as the immunogen, a-D-mannopyranoside. The Abs that recognize mimicry appear to bind to a common epitope on the peptide and do not share the mode of peptide binding with Con A. Binding kinetics and thermodynamics of Ag recognition suggest that the Ab that does not recognize peptide-carbohydrate mimicry probably has a predesigned mannopyranoside-complementing site. In contrast, the mimicry-recognizing Abs adopt the Ag-combining site only on exposure to the sugar, exploiting the conformational flexibility in the CDRs. Although the mAb 1H7 showed unique specificity toward mannopyranoside, the mimicry-recognizing Abs 2D10 and 1H11 exhibited degenerate specificities with regard to other sugar moieties. It is proposed that the degeneracy of specificity arising from the plasticity at the Ag-combining site in a subset of the Ab clones may be responsible for exhibiting molecular mimicry in the context of Ab response.

Item Type:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:52484
Deposited On:04 Aug 2011 08:01
Last Modified:04 Aug 2011 08:03

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