A highly conserved interspecies V(H) in the human genome.
Idiotype conservation between human and mouse antibodies has been observed in association with various infectious and autoimmune diseases. We have isolated a human anti-idiotypic antibody to a mouse monoclonal anti-IgE antibody (BSW17) suggesting a conserved interspecies idiotype associated with an anti-IgE response. To find the homologue of BSW17 in the human genome we applied the guided selection strategy. Combining V(H) of BSW17 with a human V(L) repertoire resulted in three light chains. The three V(L) chains were then combined with a human V(H) repertoire resulting in three clones specific for human IgE. Surprisingly, one clone, Hu41, had the same epitope specificity and functional in vitro activity as BSW17 and V(H) complementarity-determining regions identical with that of BSW17. Real-time PCR analysis confirmed the presence of the Hu41 V(H) sequence in the human genome. These data document the first example of the isolation of a human antibody where high sequence similarity to the original murine V(H) sequence is associated with common antigen and epitope specificity.
Vogel
Monique
M
Institute of Immunology, Sahli Haus 2, Inselspital, 3010 Bern, Switzerland. monique.vogel@dkf6.unibe.ch
Tschopp
Cornelia
C
Bobrzynski
Tomasz
T
Fux
Michaela
M
Stadler
Michael B
MB
Miescher
Sylvia M
SM
Stadler
Beda 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; D017124:Conserved Sequence; D000939:Epitopes / Q000276:immunology; D015894:Genome, Human; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases