PMID: 7537978Jan 1, 1994Paper

Immunogenicity of human recombinant acetylcholine receptor alpha subunit: cytoplasmic epitopes dominate the antibody response in four mouse strains

Autoimmunity
J PalaceJ Newsom-Davis

Abstract

In mysathenia gravis (MG) autoantibodies directed against acetylcholine receptors (AChR), at the neuromuscular junction lead to muscle weakness. These antibodies are directed against extracellular determinants, predominantly on the AChR alpha subunits. Similar antibodies can be induced in animals by immunisation with purified AChR, but immunisation of mice with recombinant human alpha subunit or its extracellular domain has produced conflicting results. To study further the immunogenicity of the human alpha subunit we immunised four inbred stains (C57B1/6, SJL, BALB/c, SWR) with almost full-length recombinant alpha subunit, r37-429, and looked at B cell epitopes by mapping with smaller recombinant fragments and synthetic peptides. The majority of anti-r37-429 antibodies bound to sequences within a region thought to be cytoplasmic, alpha 325-368, and reacted with human AChR. In two C57B1/6 sera, only, most antibodies were directed against an extracellular region, alpha 138-167, but the r37-429 used for immunisation of these two mice appeared to have lost the integrity of its cytoplasmic domain during preparation. Our results suggest that the antigenicity of the cytoplasmic region of the recombinant alpha subunit dominates the im...Continue Reading

References

Jan 1, 1976·Annals of the New York Academy of Sciences·V A LennonM E Seybold
Feb 26, 1986·Biochemical and Biophysical Research Communications·M C SouroujonS Fuchs
Jan 1, 1987·Annals of the New York Academy of Sciences·D B DrachmanA Pestronk
Jan 1, 1988·Advances in Immunology·J LindstromY Fujii
Dec 1, 1985·Journal of Neurology, Neurosurgery, and Psychiatry·A Vincent, J Newsom-Davis

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Citations

Jan 1, 1994·Advances in Neuroimmunology·A Vincent
Nov 18, 2000·European Journal of Biochemistry·A VincentB Lang
Aug 23, 2011·Journal of Forensic Sciences·Sara J FloodJohn McGeachie

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