Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease.
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 Vkappa light chain whereas 75.6% shows a light chain of Vlamda origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vkappa 1-39 and Vlambda 1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/kappa and T13/lambda variable regions demonstrated a more restricted antigen recognition on T13/lambda than on T2/kappa. 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 lambda as well as kappa 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.
Bresson
D
D
CNRS-UMR 5094, Faculté de Pharmacie, 15 avenue charles Flahault, 34060 Montpellier, France.
Chardès
T
T
Chapal
N
N
Bès
C
C
Cerutti
M
M
Devauchelle
G
G
Bouanani
M
M
Mani
J C
JC
Péraldi-Roux
S
S
D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D006111:Graves Disease / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology*; D007453:Iodide Peroxidase / Q000276:immunology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011994:Recombinant Proteins; D007453:Iodide Peroxidase