Mechanisms by which the I-A(BM12) 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

Abstract

The I-A(bm12) mutation in C57B1/6 (B6) mice yields the B6.C-H-2(bm12) (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 α subunit which dominate the CD4+ cell sensitization in B6 mice. We immunized with TAChR bm12, B6 and (bm12xB6)F1 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 F1 mice were challenged with TAChR and α subunit epitope peptides, using F1, B6 or bm12 APC. B6 and F1 APC presented all these Ag efficiently, while bm12 APC presented TAChR and peptide Tα150-169 poorly and erratically. Anti-TAChR and anti-α subunit epitope CD4+ lines propagated from F1 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 F1 mice had a strong preferential usage of Vβ6. Anti-Tα150-169 lines from F1 mice had also a slightly higher Vβ14 usage. B6, bm12 and F1 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 Tα150-160, consequent to the inability of the I-A(bm12) molecule to present this sequence.

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

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Mechanisms by which the I-A(BM12) mutation influences susceptibility to Experimental Myasthenia Gravis: A study in homozygous and heterozygous mice'. Together they form a unique fingerprint.

Cite this