T cell responses to human recombinant acetylcholine receptor‐α subunitin myasthenia gravis and controls

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Abstract
Antibodies against the nicotinic acetylcholine receptor (AChR) of the neuro-muscular junction are detectable in most patients with myasthenia gravis (MG) and assumed to participate in the destruction of the AChR, thereby, causing the characteristic signs and symptoms of the disease. The extent and importance of T cell responses to AChRand its subunits in MG are still unsettled. We have now examined T cell reactivities using human recombinant AChR-α subunit as antigen. Upon recognition of appropriate antigen in an MHC-class II-restricted fashion, memory T cells secrete interferon-γ (IFN-γ). Adopting this principle in an immunospot assay we found that 73% of MG patients had recombinant human AChR-α subunit-reactive T cells at a median value of 1 per 56000 blood mononuclear cells, while only 27% of the MG patients responded to the α subunit in a conventionallymphocyte proliferation assay. This compares with even lower numbers of AChR-reactive T cells and 14% positivity in the proliferation assay among control subjects. The T cell responses to the control antigens purified protein derivative and myelin basicprotein did not differ between MG and controls, underlining the specificity of an augmented T cell reactivity to AChR-α subunit in MG. α Subunit-specific T cell lines and clones propagated from patients with MG and healthy controls yielded a high proportion of α subunit-reactive T cells in the IFN-γ immunospot aassay. Their appearance was inhibited by the addition of monoclonal anti-MHC class II antibodies, demonstrating that an MHC-restricted T cell response was measured. Our data underline that the AChR-α subunit is a major T cell autoantigen in MG.

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