科研之友
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摘要
The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein, These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established, We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [I-125]alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR, Two Fab strongly inhibited binding of mAb to the main immunogenic region on the a subunits and one Fab bound to an epitope on the fetal-specific gamma subunit, In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor, The closest germline counterparts for their heavy chains were in V-H families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse a cell clones, The combinatorial approach holds promise for further analysis of human autoantibodies.
- 出版日期1997-9
