PMID: 9434796Jan 22, 1998Paper

How subtle differences in MHC class II affect the severity of experimental myasthenia gravis

Clinical Immunology and Immunopathology
B YangD B Drachman

Abstract

Myasthenia gravis is an autoimmune disorder characterized by muscle weakness, due to an antibody-mediated deficit of acetylcholine receptors (AChRs) at neuromuscular junctions. We analyzed the factors that determine the severity of experimental myasthenia gravis (EAMG) induced by immunization with Torpedo AChR, in two congenic strains of mice--B6 mice, which are highly susceptible to EAMG; and bm12 mice, which are relatively resistant, and differ only in a change of three amino acids in MHC Class II. We prepared large numbers of AChR-specific T cell hybridomas from each strain and characterized their epitope specificities and T cell receptor (TCR) gene usage: Half the B6 hybridomas responded to a single AChR peptide (alpha 146-162), and their TCR genes encoded restricted V alpha and V beta chains and CDR3 motifs. bm12 hybridomas had different epitope specificities and different, less restricted TCR genes. APCs were able to present AChR or AChR-derived peptides virtually exclusively to hybridomas of their own strain. Levels of antibodies to Torpedo and autoantibodies to mouse AChR were higher in B6 mice, and were biased toward the IgG2b isotype. We conclude that the "better fit" of MHC II, peptide, and TCR in the B6 mice enhance...Continue Reading

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Citations

Oct 8, 1999·Annals of Neurology·D B Drachman
Jul 29, 1999·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H B WangF D Shi
Jul 21, 1998·Annals of the New York Academy of Sciences·D B DrachmanB Yang
Mar 19, 2014·PloS One·Gisela Nogales-GadeaIsabel Illa
Jan 22, 2003·The Journal of Investigative Dermatology·S J P WarrenL A Diaz
Dec 21, 2012·Annals of the New York Academy of Sciences·Erdem TüzünPremkumar Christadoss
May 25, 2006·Human Immunology·Güher Saruhan-DireskeneliFeza Deymeer
Dec 11, 2002·Journal of Autoimmunity·Rui-Sheng DuanBao-Guo Xiao
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sue StacyEllen Kraig
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathan E StandiferAnthony J Infante

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