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Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease

Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in... Forty-one single-chain variable region fragments (scFvs) directed against thyroid peroxidase (TPO) were obtained by phage display libraries constructed from thyroid-infiltrating B cells of Graves’ disease patients. Among these scFvs, 24.4% used a Vκ light chain whereas 75.6% shows a light chain of Vλ origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vκ1-39 and Vλ1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/κ and T13/λ variable regions demonstrated a more restricted antigen recognition on T13/λ than on T2/κ. These two recombinant antibodies, expressed as whole IgG1 in the baculovirus/insect cell system, inhibited the binding to TPO of serum TPO autoantibodies whatever the light chain. Our study indicates thatλ as well as κ light chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Antibodies IOS Press

Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease

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Publisher
IOS Press
Copyright
Copyright © 2001 by IOS Press, Inc
ISSN
1093-2607
eISSN
1875-869X
Publisher site
See Article on Publisher Site

Abstract

Forty-one single-chain variable region fragments (scFvs) directed against thyroid peroxidase (TPO) were obtained by phage display libraries constructed from thyroid-infiltrating B cells of Graves’ disease patients. Among these scFvs, 24.4% used a Vκ light chain whereas 75.6% shows a light chain of Vλ origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vκ1-39 and Vλ1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/κ and T13/λ variable regions demonstrated a more restricted antigen recognition on T13/λ than on T2/κ. These two recombinant antibodies, expressed as whole IgG1 in the baculovirus/insect cell system, inhibited the binding to TPO of serum TPO autoantibodies whatever the light chain. Our study indicates thatλ as well as κ light chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease.

Journal

Human AntibodiesIOS Press

Published: Jan 1, 2001

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