Mimicry of human IgE epitopes by anti-idiotypic antibodies.
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.
Vogel
M
M
Institute of Immunology and Allergology, Sahli Haus 2, Inselspital, 3010, Switzerland.
Miescher
S
S
Kuhn
S
S
Zürcher
A W
AW
Stadler
M B
MB
Ruf
C
C
Effenberger
F
F
Kricek
F
F
Stadler
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D018448:Models, Immunological; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019151:Peptide Library; D011817:Rabbits; D016415:Sequence Alignment
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D019151:Peptide Library; D007073:Immunoglobulin E