Mechanisms by which the I‐ABM12 Mutation Influences Susceptibility to Experimental Myasthenia Gravis: a Study in Homozygous and Heterozygous Mice

P. I. KARACHUNSKI, N. OSTLIE, M. BELLONE, A. J. INFANTE, B. M. CONTI‐FINE

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The I‐Abm12 mutation in C57B1/6 (B6) mice yields the B6. C‐H‐2bm12 (bm12) strain, which is resistant to Experimental Myasthenia Gravis (EMG) induced by immunization with Torpedo acetylcholine receptor (TAChR), while the parental B6 strain is highly susceptible to EMG. CD4+ cells from bm12 mice immunized with TAChR do not recognize three sequence regions of the TAChR Q subunit which dominate the CD4+ cell sensitization in B6 mice. We immunized with TAChR bm12, B6 and (bm12B6)Fl mice. B6 and F1 mice developed EMG with comparable frequency. Their CD4+ cells recognized the same TAChR α subunit peptide sequences (Tα150–169, Tα181–200 and Tα360–378). CD4+ cells from TAChR‐sensitized Fl mice were challenged with TAChR and α subunit epitope peptides, using F1, B6 or bml 2 APC. B6 and F1 APC presented all these Ag efficiently, while bm 12 APC presented TAChR and peptide Tα150–169 poorly and erratically. Anti‐TAChR and anti‐α subunit epitope CD4+ lines propagated from Fl and B6 mice had similar TcR Vβ usage. All lines but those specific for the sequence Tα150–169 had unrestricted Vβ usage. Anti‐Tα150–169 lines from both B6 and Fl mice had a strong preferential usage of Vβ6. Anti‐Tα150–169 lines from Fl mice had also a slightly higher Vβ14 usage. B6, bm12 and Fl mice developed similar anti‐TAChR Ab titres, and had Ab bound to muscle AChR in comparable amounts. Therefore EMG resistance of bm12 mice must be due to a subtle shift in the anti‐AChR Ab repertoire, and absence of special Ab able to cause destruction and/or dysfunction of muscle AChR. This is probably related to the absence of CD4+ cells sensitized to epitopes within the sequence Tα 150–160, consequent to the inability of the I‐Abm12 molecule to present this sequence.

Original languageEnglish (US)
Pages (from-to)215-225
Number of pages11
JournalScandinavian Journal of Immunology
Volume42
Issue number2
DOIs
StatePublished - Aug 1995

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Mechanisms by which the I‐ABM12 Mutation Influences Susceptibility to Experimental Myasthenia Gravis: a Study in Homozygous and Heterozygous Mice'. Together they form a unique fingerprint.

Cite this