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

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.