CLONING OF A HUMAN AUTOIMMUNE-RESPONSE - PREPARATION AND SEQUENCING OF A HUMAN ANTITHYROGLOBULIN AUTOANTIBODY USING A COMBINATORIAL APPROACH

被引：27

作者：

HEXHAM, JM

FURMANIAK, J

PEGG, C

BURTON, DR

SMITH, BR

机构：

[1] Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield

[2] Endocrine Immunology Unit, Department of Medicine, University of Wales College of Medicine, Cardiff

[3] Department of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA

来源：

AUTOIMMUNITY | 1992年 / 12卷 / 02期

基金：

英国医学研究理事会;

关键词：

HASHIMOTO DISEASE; THYROID AUTOANTIBODIES; IMMUNE REPERTOIRES; COMBINATORIAL LIBRARIES; THYROGLOBULIN;

D O I：

10.3109/08916939209150320

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Thyroid lymphocyte RNA from a Hashimoto patient exhibiting high titre serum IgG autoantibodies against thyroglobulin (Tg) has been used to construct a Fab library in phage lambda. Screening of this library with radioiodinated Tg has permitted the cloning of an anti-Tg antibody (MH52) with an affinity of 4.5x10' molar1 as determined by inhibition ELISA. Sequence analysis showed MH52 to be an authentic antibody of the IgGl/K isotype with variable region genes from the VHI and VKIII families in combination with the JH3, DK4 and JK2 gene segments. The MH52 light chain gene showed high sequence homology (93% with the germline gene used by several rheumatoid factors and some DNA autoantibodies. Greater divergence from the germline was observed in the case of the MH52 heavy chain gene which showed 86% homology with a germline heavy chain gene isolated from human liver. Overall the similarity between the genes coding for MH52 and the genes coding for some other autoantibodies of non-related specificity might suggest that similar regulatory processes control the formation of these different autoantibodies. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：135 / 141

页数：7

共 22 条

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