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Antigenic modulation and receptor loss in experimental autoimmune myasthenia gravis
Author(s) -
Lindstrom Jon,
Einarson Brett
Publication year - 1979
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880020304
Subject(s) - acetylcholine receptor , receptor , antibody , myasthenia gravis , endocytosis , chemistry , antigen , in vivo , biology , endocrinology , medicine , microbiology and biotechnology , biochemistry , immunology
Immunization of groups of rats with 0.1–100 μg of acetylcholine receptor (AChR) purified from the electric organ of Torpedo californica resulted in dose‐dependent (1) loss of acetylcholine receptor from the rats' muscles, (2) binding of antibodies to many of the receptors remaining in muscle, and (3) production of antibodies in serum capable of cross‐reacting with receptor solubilized from rat muscle. Addition of antibodies from rats immunized with electric organ acetylcholine receptors to muscle cells in culture caused loss of receptor by accelerating the rate of receptor degradation. Monovalent antibody fragments did not accelerate degradation unless antiantibody was added to cross‐link the monovalent antibody fragments bound to receptors. This indicates that cross‐linking of receptors by antibody molecules triggers accelerated receptor degradation, leading to receptor loss. The rate of increase in receptor destruction due to antigenic modulation observed in vitro appears sufficient to account for the extent of receptor loss observed in vivo. Endocytosis of antibody cross‐linked receptors may be a rate‐limiting step common to antigenic modulation in vitro and in vivo.