title: Major histocompatibility complex class II gene disruption prevents experimental autoimmune myasthenia gravis.
abstract: To analyze the impact of lack of MHC class II gene expression, and to demonstrate the direct genetic evidence for the involvement of the MHC class II gene product in the development of experimental autoimmune myasthenia gravis (EAMG), MHC class II gene-disrupted C57BL6 mutant (-/-) and EAMG-susceptible MHC class II wild-type C57BL6 mice (+/+) were evaluated for the clinical and immunopathologic manifestations of EAMG. The deficiency of MHC class II, and therefore, CD4+ T cells, completely prevented the C57BL6 MHC class II mutant (-/-) mice from mounting an autoimmune response to the nicotinic acetylcholine receptor. Further, the mutant (-/-) mice failed to show any immunopathologic and clinical manifestations of EAMG. The data unequivocally provide direct genetic evidence for the essential role of MHC class II molecules in the induction of EAMG, and rule out any pathogenic effector role for MHC class I-restricted CD8+ T cells, gamma delta TCR-bearing cells, or NK cells, which are intact in the MHC class II mutant mice in the induction of EAMG.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555.
authors.forename: R
authors.initials: R
authors.lastname: Kaul
authors.forename: M
authors.initials: M
authors.lastname: Shenoy
authors.forename: E
authors.initials: E
authors.lastname: Goluszko
authors.forename: P
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015704:CD4 Antigens / Q000502:physiology; D005802:Genes, MHC Class II; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009157:Myasthenia Gravis / Q000517:prevention & control*; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015704:CD4 Antigens; D011950:Receptors, Cholinergic