Prediction of the interacting surfaces in a trimolecular complex formed between the major dust mite allergen Der p 1, a mouse monoclonal anti-Der p 1 antibody, and its anti-idiotype

P B Furtado¹, R Furmonaviciene¹, J McElveen¹, H F Sewell¹ and F Shakib¹

¹ Division of Molecular and Clinical Immunology, University of Nottingham, Faculty of Medicine and Health Sciences, Nottingham NG7 2UH, UK

Correspondence to:
Dr Shakib farouk.shakib{at}nottingham.ac.uk

Background—Two mouse monoclonal antibodies (mAbs) have been described recently; namely, mAb 2C7 (IgG2b), which is directed against the major house dust mite allergen Der p 1, and mAb 2G10 (IgG1), which is an anti-idiotypic antibody raised against mAb 2C7. The anti-idiotype mAb 2G10 does not block the binding of mAb 2C7 to Der p 1, which means that mAb 2C7 can simultaneously bind to Der p 1 and to mAb 2G10, thereby generating a trimolecular complex consisting of antigen–idiotype–anti-idiotype.

Aims—To sequence and model the V region of the anti-idiotypic antibody mAb 2G10 to enable the prediction of the interacting surfaces in the trimolecular complex consisting of Der p 1–mAb 2C7–mAb 2G10.

Methods—DNA sequencing of mAb 2G10 was carried out and the Swiss Model and Swiss PDB-Viewer programs were used to build a three dimensional model of the trimolecular complex.

Results—Complementarity of shape and charge was revealed when comparing the protrusion of the previously determined Der p 1 epitope (Leu147–Gln160) with the cavity formed by the complementarity determining regions (CDRs) of mAb 2C7. Such complementarity was also observed between the mAb 2C7 epitope predicted to be recognised by mAb 2G10 (residues Lys19 from framework region 1 (FRW1) and Ser74–Gln81 from FRW3) and residues from the CDRs of mAb 2G10 (a negatively charged patch flanked by the residues Asp55H/Glu58H and Glu27L/Glu27cL). As expected, the location of the mAb 2C7 epitope recognised by mAb 2G10 does not appear to interfere with the binding of Der p 1 to mAb 2C7.

Conclusion—Although the results obtained represent only an approximation, they nevertheless provide a rare insight into how an antigen (Der p 1) might bind to its antibody (mAb 2C7) while in complex with an anti-idiotype (mAb 2G10).

Key Words: Der p 1 • anti-idiotype antibodies • monoclonal antibodies • antigen-antibody binding

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• Furtado, P B, McElveen, J E, Gough, L, Armour, K L, Clark, M R, Sewell, H F, Shakib, F (2002). The production and characterisation of a chimaeric human IgE antibody, recognising the major mite allergen Der p 1, and its chimaeric human IgG1 anti-idiotype. Mol. Pathol. 55: 315-324 [Abstract] [Full Text]