The autoimmune response of different mouse strains to T-cell epitopes of the human acetylcholine receptor alpha subunit.
The specific recognition of the acetylcholine receptor and its alpha-subunit by T cells derived from patients with myasthenia gravis or mice with experimental autoimmune myasthenia gravis raises the question of the role of autoreactive T cells in the myasthenic process. Sequences of the acetylcholine receptor alpha-subunit previously shown to be immunogenic in myasthenic patients were tested for their immunogenicity in various inbred mouse strains. High, intermediate and low T-cell proliferative responses could be observed to peptides representing sequences 195-212 and 259-271 of the human acetylcholine receptor alpha-subunit. Following immunization with the Torpedo acetylcholine receptor, lymphocytes of SJL mice proliferated efficiently to p 195-212 but not to p259-271. On the other hand, lymph node cells of BALB/c mice responded well to p259-271 but not to p195-212. Thus, the influence of the genetic make-up of the examined mice on the immune response to the two peptides could be clearly demonstrated by the existence of strain-dependent immunodominant and cryptic regions on the autoantigen. The differences between the strains were less pronounced when antibody responses were measured to these two T-cell epitopes, although a partial correlation with the proliferative responses could be observed. It can be concluded that epitopes specifically recognized by T lymphocytes of patients with myasthenia gravis also represent specific T-cell epitopes in the autoreactivity to the acetylcholine receptor in mice and that immune responsiveness to these peptides is influenced by the genetic make-up of the responding mouse strains.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
S
S
Brocke
M
M
Dayan
J
J
Rothbard
S
S
Fuchs
E
E
Mozes
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011950:Receptors, Cholinergic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D011950:Receptors, Cholinergic