Experimental myasthenia gravis in congenic mice. Sequence mapping and H-2 restriction of T helper epitopes on the α subunits of Torpedo californica and murine acetylcholine receptors

M. Bellone, N. Ostlie, S. Lei, B. M. Conti-Tronconi

Research output: Contribution to journalArticlepeer-review

Abstract

Immunization of mice with nicotinic acetylcholine receptor from Torpedo electric organ (TAChR) causes a disease similar to human myasthenia gravis (experimental autoimmune myasthenia gravis, EAMG). Susceptibility to EAMG correlates with the H-2 haplotype. In this study we used overlapping synthetic peptide corresponding to the complete sequences of the α subunits from TAChR and murine muscle AChR (MAChR) to map T helper epitopes in congenic murine strains of different H-2 haplotype. C57BL/6 and BALB/B mice (highly susceptible to EAMG) and BALB/c and CB17 mice (less susceptible to EAMG), immunized with TAChR, developed similar anti-TAChR antibody titers and L3T4+ (T helper) cell sensitization. Different sequence segments of the TAChR α subunit were recognized by L3T4+ cells from strains of H-2b and H-2(d) haplotype. The sequence segments recognized by the H-2(d) strains have the highest predicted propensity to form amphipatic α helices, while those recognized by the H-2b strains do not. We investigated whether in EAMG T helper cells cross-react with autologous AChR sequences, and a true break of the tolerance occurs. Overlapping synthetic peptides, corresponding to the complete sequence of MAChR α subunit, were used to test L3T4+ cell from mice immunized with TAChR. L3T4+ cell from H-2b strains did not cross-react with any murine peptide sequence, while L3T4+ cells from H-2(d) mice were strongly stimulated by the peptide sequence Mα 304-322, which is very similar to the homologous Torpedo peptide.

Original languageEnglish
Pages (from-to)2303-2310
Number of pages8
JournalEuropean Journal of Immunology
Volume21
Issue number10
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Immunology

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