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

Adrian A. Lobito, Bingzhi Yang, Marcela F. Lopes, Alexei Miagkov, Robert N. Adams, Gregory R. Palardy, Michele M. Johnson, Hugh I. McFarland, Michael Recher, Daniel B. Drachman, Michael J. Lenardo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2055-2067
Number of pages13
JournalEuropean Journal of Immunology
Volume32
Issue number7
DOIs
StatePublished - 2002

Keywords

  • Antibody
  • B cell
  • Experimental autoimmune myasthenia gravis
  • Myasthenia gravis
  • TCR transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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