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.
BACKGROUND
Two mouse monoclonal antibodies (mAbs) have been described recently; namely, mAb 2C7 (IgG2b kappa), which is directed against the major house dust mite allergen Der p 1, and mAb 2G10 (IgG1 kappa), 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.


OBJECTIVE
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.


CONCLUSIONS
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).
Furtado
P B
PB
Division of Molecular and Clinical Immunology, University of Nottingham, Faculty of Medicine and Health Sciences, Nottingham NG7 2UH, UK.
Furmonaviciene
R
R
McElveen
J
J
Sewell
H F
HF
Shakib
F
F
D000485:Allergens / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D039741:Antigens, Dermatophagoides; D001483:Base Sequence; D022801:Complementarity Determining Regions; D018076:DNA, Complementary / Q000235:genetics; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008925:Mites / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D039741:Antigens, Dermatophagoides; D022801:Complementarity Determining Regions; D018076:DNA, Complementary; D006023:Glycoproteins; D007073:Immunoglobulin E