Thyroid peroxidase autoantibodies obtained from random single chain FV libraries contain the same heavy/light chain combinations as occur in vivo

Endocrinology
Nicolas ChapalSylvie Péraldi-Roux

Abstract

Three combinatorial libraries were constructed from unpurified, CD19(+), and antithyroid peroxidase (anti-TPO) B cells extracted from thyroid tissue of Graves' disease patients. Fifteen of the 41 randomly derived anti-TPO single chain variable region fragments (scFvs), showed VH1-3/V lambda 1-51 or VH1-69/V lambda 1-40 heavy/light chain pairing similar to that obtained with TPO-specific scFv derived from an in-cell library. One VH1-3/V lambda 1-51 scFv, A16, showed exactly the same nucleotide sequence as in-cell scFv ICB7, demonstrating that in vivo rearrangement can be obtained from a random combinatorial library. The majority of the scFvs used a heavy chain gene derived from the VH1-3 gene segment, whereas the light chain gene segments used were more heterogeneous, with dominance of the V kappa 1-39 and V lambda 1-51 gene segments. The anti-TPO scFvs showed high affinities to TPO, with values between 0.77 and 12.3 nM, and defined seven antigenic regions on the TPO molecule. The anti-TPO fragments, particularly VH1-3/V lambda 1-51 randomly associated scFv B4, which mimic natural H/L pairing, and VH1-3/V lambda 1-40 in-cell-derived scFv ICA5, efficiently displaced the TPO binding of serum autoantibodies from 20 Graves' disease ...Continue Reading

Citations

Feb 4, 2011·Science Translational Medicine·Damien Bresson, Matthias von Herrath
Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Mar 28, 2008·Clinical Endocrinology·Sandra M McLachlan, Basil Rapoport
Jun 1, 2006·International Immunology·Sandra A RebuffatSylvie Péraldi-Roux
Sep 8, 2007·Thyroid : Official Journal of the American Thyroid Association·Sandra M McLachlan, Basil Rapoport
Jan 10, 2003·The Journal of Clinical Endocrinology and Metabolism·Francesco LatrofaSandra M McLachlan
Jul 30, 2005·Arthritis and Rheumatism·Iftikhar A ChowdhryBetty Diamond
Mar 17, 2005·Journal of Autoimmune Diseases·Damien BressonSylvie Péraldi-Roux

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