Mapping myasthenia gravis–associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice

Human thyroglobulin peptide p2340 induces autoimmune thyroiditis in HLA-DR3 transgenic mice

“…In all the transgenic mice, expression of HLA class II and absence of endogenous MHC class II molecules were verified by FACS and PCR [10]. The percentage of CD4C and CD8C cells in the peripheral blood leucocytes of DR3 mice was analysed before immunization by flow cytometry [17]. The results showed that the immune system in HLA transgenic mice developed normally, with appropriate expression and functionality of MHC class II molecules.…”

Acetylcholine Receptor-Induced Experimental Myasthenia Gravis: What Have We Learned from Animal Models After Three Decades?

“…Moreover, EAMG rats, orally treated during the acute and chronic phase with a human recombinant extracellular domain of the AChR a-subunit (Ha1-205), are similarly tolerized. This treatment results in a shift from Th1 to Th2 response and from IgG2 to IgG1 Abs IFN-c -/-mice do not develop muscle weakness Balasa et al (1997) IL-2 -/-mice show a reduction in Th1 cell response and anti-AChR IgG2a Abs Moiola et al (1998) IFN-cR -/-mice develop lower incidence and disease severity Zhang et al (1999) IL-4 -/-mice appear more susceptible to the disease Karachunski et al (1999) Absence of IFN-c or IL-12 has different effects on EAMG induction Karachunski et al (2000) HLA-DQ6 transgenic mice are resistant to develop the disease Poussin et al (2001) IL-6 -/-mice develop resistance to the disease Deng et al (2002) EAMG susceptibility is associated to expression of HLA-DQ8 and DR3 molecules Yang et al (2002) TNF-R p55 -/-p75 -/-mice are protected to development of EAMG Goluszko et al (2002) Single immunization induces muscle weakness in IL-4 -/-mice Ostlie et al (2003) STAT4 -/-and STAT6 -/-BALB/c mice acquire susceptibility to EAMG Wang et al (2004) T-bet deficiency decreases the susceptibility to the disease Liu et al (2009) Aire-depleted mice are differently susceptible depending on age Aricha et al (2011) isotypes, and improvement of the disease ). Similar evidence is observed after oral administration of Ta146-162 synthetic peptide, corresponding to the immunodominant epitope of TAChR a-subunit, to mice immunized with TAChR.…”

Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile

“…Ta 146-162 (Leu-Gly-Ile-Trp-Thr-Tyr-Asp-Gly-TluLys-Val-Ser-Ile-Ser-Pro-Glu-Ser) peptide was synthesized at the GL Biochem (Shanghai, China) and purified by HPLC to [95% purity. TAChR and mouse AChR were purified from the electric organ of Torpedo or mouse muscle by neurotoxin affinity column [13,14]. Complete Freund's adjuvant was obtained from Sigma-Aldrich.…”

“…Mice were evaluated for clinical EAMG, and their muscle weakness was graded as follows [13]: grade 0: normal strength without any muscle weakness; grade 1: definite weakness of the forelimbs with a characteristic hunched, chin-down posture and flaccid tail after exercise involving 20-30 consecutive paw grips on the top steel grids of the animal cage; grade 2: grade 1 weakness at rest; and grade 3: severe weakness with paralysis involving all the limbs (quadriplegia) accompanied by dehydration and moribund state. On day 70, 24 mice that had developed clinical EAMG clinical scores of 1 to 2 were randomly allotted into two groups, each with equivalent grades.…”