T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor

Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions o...

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Bibliographic Details
Published in:European journal of immunology 2002-07, Vol.32 (7), p.2055-2067
Main Authors: Lobito, Adrian A., Yang, Bingzhi, Lopes, Marcela F., Miagkov, Alexei, Adams, Robert N., Palardy, Gregory R., Johnson, Michele M., McFarland, Hugh I., Recher, Michael, Drachman, Daniel B., Lenardo, Michael J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibody
B cell
B-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell Division
Epitopes, T-Lymphocyte - immunology
Experimental autoimmune myasthenia gravis
Gene Expression
Immunodominant Epitopes - immunology
Lymphocyte Count
Lymphocytic choriomeningitis virus - immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Myasthenia gravis
Myasthenia Gravis, Autoimmune, Experimental - immunology
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, alpha-beta - immunology
Receptors, Cholinergic - immunology
TCR transgenic
Torpedo
Vesicular stomatitis Indiana virus - immunology
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Summary:Myasthenia gravis (MG) is an autoimmune disease caused by T cell‐dependent antibody‐mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of α and β T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146–162 from the α subunit of TAChR presented in the context of I‐Ab to generate TCR‐transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild‐type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti‐TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti‐TAChR titers equal to B6 mice and a predominance of Th1‐induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG.
ISSN:0014-2980
1521-4141
DOI:10.1002/1521-4141(200207)32:7<2055::AID-IMMU2055>3.0.CO;2-Q