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.
BACKGROUND
Two mouse monoclonal antibodies have been described, namely: mAb 2C7 (IgG2bkappa), which is directed against the major house dust mite allergen Der p 1, and mAb 2G10 (IgG1kappa), which is an anti-idiotypic antibody raised against mAb 2C7. Given its broad IgE specificity, anti-idiotype mAb 2G10 could potentially have immunomodulatory applications. For example, a chimaeric human IgG version of mAb 2G10 could prove to be a useful molecule for binding to mast cell and basophil FcepsilonRI bound IgE, and in doing so co-ligating FcepsilonRI with FcgammaRIIB, which has been reported to have downregulatory effects.


OBJECTIVE
To produce a chimaeric human IgE version of mAb 2C7 (mAb 2C7huE) and a chimaeric human IgG1 version of its anti-idiotype mAb 2G10 (mAb 2G10huG1).


METHODS
The Vkappa and VH regions of mAb 2C7 and its anti-idiotype mAb 2G10 were engineered into human constant regions of the IgE and IgG1 isotypes, respectively.


RESULTS
The production of chimaeric mAb 2C7huE and its anti-idiotype mAb 2G10huG1 confirmed that the respective mouse antibody V regions were successfully engineered into human constant regions and still retained the specificity of the original murine V regions.


CONCLUSIONS
The newly constructed chimaeric antibodies will be useful to investigate the downregulation of IgE mediated hypersensitivity by the crosslinking of FcepsilonRI with FcgammaRIIB.
D000485:Allergens / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000918:Antibody Specificity; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D003546:Cysteine Endopeptidases; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology; D014162:Transfection
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1