TY - JOUR
T1 - T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis
T2 - Epitopes on the γ and δ subunits
AU - Manfredi, Angelo A.
AU - Protti, Maria Pia
AU - Dalton, Mark W M
AU - Howard, James F.
AU - Conti-Tronconi, Bianca M.
PY - 1993/8
Y1 - 1993/8
N2 - We tested the response of CE4+ cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the γ and δ subunits of human muscle acetylcholine receptor (AChR). The γ subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an ε subunit. The δ subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic γ subunit. Anti-AChR CD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the γ and δ subunits and had severe symptoms. In four patients the CD4+ cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected.
AB - We tested the response of CE4+ cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the γ and δ subunits of human muscle acetylcholine receptor (AChR). The γ subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an ε subunit. The δ subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic γ subunit. Anti-AChR CD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the γ and δ subunits and had severe symptoms. In four patients the CD4+ cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected.
KW - Autoimmunity
KW - Embryonic acetylcholine receptor
KW - T epitopes
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M3 - Article
C2 - 7688757
AN - SCOPUS:0027176664
VL - 92
SP - 1055
EP - 1067
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 2
ER -