TY - JOUR
T1 - Myasthenia gravis
T2 - Residues of the α and γ subunits of muscle acetylcholine receptor involved in formation of immunodominant CD4+ epitopes
AU - Moiola, Lucia
AU - Protti, Maria Pia
AU - McCormick, Daniel
AU - Howard, James F.
AU - Conti-Tronconi, Bianca M.
PY - 1994/5/1
Y1 - 1994/5/1
N2 - We propagated from myasthenia gravis (MG) patients by stimulation in vitro with synthetic sequences (α48-67, α304-322, γ75-94 and γ321-340) of the human muscle acetylcholine receptor (AChR), CD4+ lines against four 20- residue sequence regions of the AChR α and γ subunits that are recognized by Th cells of most MG patients. Most lines secreted IL-2 and not IL-4, suggesting that they comprise Th1 cells. For three lines we verified that, as reported previously, AChR epitopes are presented by DR molecules: their response to the relevant peptide was abolished by anti-DR Abs. The DR molecules presenting AChR epitopes were identified by testing the response of the lines to the relevant peptide, using APC from donors homozygous for the different DR alleles of the line. We tested the lines with single residue- substituted analogues of the epitope sequence. The results of these experiments indicated that the lines were polyclonal and recognized overlapping epitopes. Their response was abolished by some substitutions, identifying residues common to all epitopes within a given region, whereas other substitutions reduced but did not obliterate the response, indicating residues included in some but not all epitopes recognized by the line. Comparison of the residues involved in epitope formation for different lines supported the conclusion that within the 20-residue immunodominant regions investigated here, the same sequence segment is involved in formation of epitopes, even in DR-discordant patients.
AB - We propagated from myasthenia gravis (MG) patients by stimulation in vitro with synthetic sequences (α48-67, α304-322, γ75-94 and γ321-340) of the human muscle acetylcholine receptor (AChR), CD4+ lines against four 20- residue sequence regions of the AChR α and γ subunits that are recognized by Th cells of most MG patients. Most lines secreted IL-2 and not IL-4, suggesting that they comprise Th1 cells. For three lines we verified that, as reported previously, AChR epitopes are presented by DR molecules: their response to the relevant peptide was abolished by anti-DR Abs. The DR molecules presenting AChR epitopes were identified by testing the response of the lines to the relevant peptide, using APC from donors homozygous for the different DR alleles of the line. We tested the lines with single residue- substituted analogues of the epitope sequence. The results of these experiments indicated that the lines were polyclonal and recognized overlapping epitopes. Their response was abolished by some substitutions, identifying residues common to all epitopes within a given region, whereas other substitutions reduced but did not obliterate the response, indicating residues included in some but not all epitopes recognized by the line. Comparison of the residues involved in epitope formation for different lines supported the conclusion that within the 20-residue immunodominant regions investigated here, the same sequence segment is involved in formation of epitopes, even in DR-discordant patients.
UR - http://www.scopus.com/inward/record.url?scp=0028346304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028346304&partnerID=8YFLogxK
M3 - Article
C2 - 7908921
AN - SCOPUS:0028346304
SN - 0022-1767
VL - 152
SP - 4686
EP - 4698
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -