Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

S Portolano; G D Chazenbalk; P Seto; J S Hutchison; B Rapoport; S M McLachlan

doi:10.1172/JCI115943

Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Thyroid Molecular Biology Unit, Veterans' Administration Medical Center, San Francisco, California 94121.

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Published in Volume 90, Issue 3 on September 1, 1992
J Clin Invest. 1992;90(3):720–726. https://doi.org/10.1172/JCI115943.
© 1992 The American Society for Clinical Investigation

Published September 1, 1992 - Version history

To characterize the nature of thyroid peroxidase (TPO) autoantibodies present in the sera of patients with autoimmune thyroid disease, we cloned three IgG1/kappa Fab fragments which bind 125I-TPO. This was accomplished by the molecular cloning and expression in bacteria of IgG gene fragments from B cells infiltrating the thyroid of a patient with Graves' disease. The three Fab fragments (SP2, SP4, and SP5) are coded for by a common heavy chain (VH1, D, JH3) and three related, but different, light chains (VK1, JK2). The SP Fab fragments bind specifically to TPO with high affinities (6 x 10(-11)-2 x 10(-10) M) comparable to those of serum TPO autoantibodies. TPO autoantibodies represented by the SP Fab fragments are present in all 11 patients studied, constitute a high proportion (36-72%) of serum TPO autoantibodies in individual patients and interact with a conformational epitope on TPO.

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Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

S Portolano, G D Chazenbalk, P Seto, J S Hutchison, B Rapoport, and S M McLachlan

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Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

S Portolano, G D Chazenbalk, P Seto, J S Hutchison, B Rapoport, and S M McLachlan

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