Affiliations: [a] CNRS-UMR 5094, Faculté de Pharmacie, 15 avenue charles Flahault, 34060 Montpellier, France | [b] INRA-CNRS UMR 5087, Laboratoire de Pathologie Comparée, 30380 Saint-Christol-Lez-Alès, France
Correspondence:
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Corresponding author: Dr. Sylvie Peraldi-Roux, Facult´e de Pharmacie, CNRS UMR 5094. Institut de Biotechnologie et Pharmacologie, 15 avenue Charles Flahault, 34060 Montpellier Cedex 2, France. Tel.: +33 4 67 548 604; Fax: +33 4 67 548 610; E-mail: [email protected].
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% whereas 75.6% 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 that λ as well as κlight chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease.
Keywords: phage-displayed antibody, κ and λ light chains, thyroid-infiltrating B lymphocytes, autoimmune thyroid disease, autoantibody
