T-cell reactivity in myasthenia gravis

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Abstract

In a proliferation assay, peripheral blood lymphocytes (PBL) from a relatively small proportion of myasthenia gravis (MG) patients and from controls responded to Torpedo acetylcholine receptor (T-AChR), which shows approximately 75% homology with the human AChR. Over 50% of MG patients responded to recombinant human AChR α-subunit (r37-437) however, compared with 9% of controls. A proportion of MG PBL respond to synthetic peptides of the extracellular portion of the human α-subunit, but only MG patients (18%) responded to the juxta-membrane sequence p257–269. MG T-cell lines raised against native T-AChR failed to respond to the synthetic peptides. These results underline the need to use human AChR sequences to test relevant T-cell reactivity in MG.

T-cell lines raised from three MG patients to human α-subunit r37-437 have shown Stimulation Index (SI) values of 3.5–22. Three clones derived from one of these had SI values of 100–500. Preliminary testing of responsiveness in one of these clones showed reactivity to several recombinant polypeptides including r37-437 and r37-181, as in the parent line. The epitope(s) within this latter sequence have not yet been identified, but the experimental approach used here should make it possible to define critical T-cell epitopes in MG, and to determine their functional relevance by investigating the ability of AChR-reactive T-cell clones to provide specific help in anti-AChR antibody production.

References (17)

  • T. Barkas et al.

    Monoclonal antibodies to the main immunogenic region of the nicotinic acetylcholine receptor bind to residues 61–76 of the α-subunit

    J. Biol. Chem.

    (1988)
  • J. Newsom-Davis

    Diseases of the Neuromuscular Junction

  • A. Vincent et al.

    Anti-acetylcholine receptor antibodies

    J. Neurol. Neurosurg. Psychiat.

    (1980)
  • A.G. Engel

    Morphologic and immunopathologic findings in myasthenia gravis and in congenital myasthenic syndromes

    J. Neurol. Neurosurg. Psychiat.

    (1980)
  • S.J. Tzartos et al.

    Localization of the main immunogenic region of human muscle acetylcholine receptor to residues 67–76 of the α subunit

  • D.A.S. Compston et al.

    Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis

    Brain

    (1980)
  • A.G. Demaine et al.

    Genetic susceptibility to myasthenia gravis studied by DNA hybrid isolation

    Ann. NY Acad. Sci.

    (1987)
  • M. Noda et al.

    Cloning and sequence analysis of calf cDNA and human genomic DNA encoding α-subunit precursor of muscle acetylcholine receptor

    Nature

    (1983)
There are more references available in the full text version of this article.

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