T Cell Responses in EAMG-Susceptible and Non-Susceptible Mouse Strains After Immunization with Overlapping Peptides Encompassing the Extracellular Part of Torpedo Californica Acetylcholine Receptor α Chain. Implication to Role in Myasthenia Gravis of Autoimmune T-Cell Responses Against Receptor Degradation Products

Abstract

To study the role in myasthenia gravis (MG) of peptides resulting from acetylcholine receptor (AChR) degradation, we examined the ability of AChR peptides to induce T cell responses that are capable of cross-reacting with intact AChR. The studies were carried out in an experimental autoimmune MG (EAMG)-susceptible mouse strain [C57BL/6 (B6)J as well as in two non-susceptible strains [B6.C-H-2bm12 (bm12) and C3H/HeJ. A set of overlapping peptides encompassing the extracellular part (residues 1-210) of the α-chain of Torpedo californica (t) AChR were used, individually or in equimolar mixtures, as immunogens. In B6, immunization with peptides α45-60, α 111-126, α 146-162 and α 182-198 gave T cells that responded in vitro to the correlate immunizing peptide. Only the T cells against the latter three peptides cross-reacted with tAChR. Peptide α 146-162 exhibited the highest in vitro reaction with the immunizing peptide and cross-reaction with tAChR. T cells obtained by immunization of B6 with an equimolar mixture of the peptides responded in vitro to peptides α 111-126, α 146-162 and α 182-198 and cross-reacted very strongly with tAChR. In bml2 and C3H/He, a number of peptides evoked, when used individually as immunogens, strong or moderate T cell responses that recognized in vitro the correlate immunizing peptide but cross-reacted poorly with tAChR. Immunization with the mixture of the peptides gave T cells that recognized several peptides in each strain but