Mimicry of human IgE epitopes by anti-idiotypic antibodies

Abstract

According to Jerne's network hypothesis, the binding site of an anti-idiotypic antibody also represents the internal image of an epitope present on a foreign, or even a self antigen. In recent years, antigen mimicry has been defined at the molecular level for some xeno-antigens. However, until now there has been no demonstration of structural mimicry between a human anti-idiotypic antibody and a self structure. To address this question, we used human IgE as the self structure and a well-defined anti-human IgE mAb (BSW17). We describe the isolation of two anti- idiotypic antibodies specific for the anti-IgE antibody BSW17 from a non-immune human Fab phage display library. Interestingly, these two anti-idiotypic antibodies mimic the same molecular surface region as a previously described IgE peptide mimotope isolated by panning on BSW17, but they cover a much larger epitope on the IgE molecule. Accordingly, immunisation of rabbits with the two anti-idiotypic antibodies induced high-affinity antibodies with the same characteristics as BSW17. Thus, our data demonstrate that it is possible to isolate anti-idiotypic antibodies derived from the human genome without the need for hyperimmunization, and confirm Jerne's hypothesis that both foreign antigens and self structures can be mimicked by our own immunoglobulins.

Label-free electronic probing of nucleic acids and proteins at the nanoscale using the nanoneedle biosensor

“…Direct electrical detection of biomolecules without the need for any labeling can help greatly advance point-of-care diagnostics. Applications include the study of virology, [1][2][3] ligand fishing, 4,5 bacteriology, 6-8 apoptosis, 9 cell biology and adhesion, 10,11 epitope mapping, [12][13][14] signal transduction, 15,16 immune regulation, 17 nucleic acid-nucleic acid interactions, [18][19][20] and nucleic acid-protein protein interactions, 21,22 and study of post-translational modifications. 23,24 Detection of proteins and nucleic acids is often performed using optical fluorescence based techniques, which are more costly and timely than electrical detection due to the need for expensive and bulky optical equipment and the process of fluorescent tagging.…”

Natural anti-FcεRIα autoantibodies may interfere with diagnostic tests for autoimmune urticaria

“…Construction of IgM Fab library LTM from CD19-positive B cells from the tonsils of 3 children (aged 5.5 1.6 years, 3-6.6 years) and selection of clones is described elsewhere [36,37]. IgM Fab library UM and IgG Fab library UG were constructed from blood B cells of two CU patients.…”

Label-free screening of bio-molecular interactions

“…These relatively novel approaches do not allow screening of extremely large numbers of compounds (high throughput screening or HTS), however they do facilitate more critical evaluation of the quality of the data generated, particularly in regard to interaction specificity and ranking of affinities. [4,5,6], virology [7,8,9], epitope mapping [10,11,12], molecular engineering [13], cell biology [14,15], cell adhesion [16,17], signal transduction [18,19], immune regulation [1], nucleotide-nucleotide [20,21,22] and nucleotide-protein [23,24] binding, and enzyme mechanisms [25,26]. Many of the commercially available optical biosensors exploit a surface-sensitive physical phenomenon called an evanescent wave.…”