Abstract:
:We have designed a 39 amino acid peptide mimic of the conformation-dependent main immunogenic region (MIR) of the Torpedo acetylcholine receptor (TAChR) that joins three discontinuous segments of the Torpedo α-subunit, α(1-12), α(65-79), and α(110 - 115) with two GS linkers: This 39MIR-mimic was expressed in E. coli as a fusion protein with an intein-chitin-binding domain (IChBD) to permit affinity collection on chitin beads. Six MIR-directed monoclonal antibodies (mAbs) bind to this complex and five agonist/antagonist site directed mAbs do not. The complex of MIR-directed mAb-132A with 39MIR has a Kd of (2.11±0.11)×10(-10)M, which is smaller than (7.13±1.20)×10(-10)M for the complex of mAb-132A with α(1-161) and about the same as 3.4×10(-10)M for that of mAb-132A with TAChR. Additionally, the 39MIR-IChBD adsorbs all MIR-directed antibodies (Abs) from an experimental autoimmune myasthenia gravis (EAMG) rat serum. Hence, the 39MIR-mimic has the potential to inactivate or remove pathogenic Torpedo MIR-directed Abs from EAMG sera and to direct a magic bullet to the memory B-cells that produce those pathogenic Abs. The hope is to use this as a guide to produce a mimic of the human MIR on the way to an antigen specific therapeutic agent to treat MG.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Trinh VB,Foster AJ,Fairclough RHdoi
10.1016/j.molimm.2014.01.002subject
Has Abstractpub_date
2014-05-01 00:00:00pages
79-90issue
1eissn
0161-5890issn
1872-9142pii
S0161-5890(14)00003-0journal_volume
59pub_type
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更新日期:1988-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0161-5890(97)00024-2
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pub_type: 杂志文章
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pub_type: 评论,信件
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pub_type: 杂志文章
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