T helper function of CD4+ cells specific for defined epitopes on the acetylcholine receptor in congenic mouse strains.
We previously identified sequence segments of Torpedo acetylcholine receptor (TAChR) alpha subunit recognized by CD4+ cells of congenic mouse strains of different H-2 haplotypes, susceptible to experimental autoimmune myasthenia gravis. CD4+ cells from BALB/c and CB17 mice (H-2d) recognized the peptide sequences alpha 1-20 and alpha 304-322, while C57BL/6 and BALB/b mice (H-2b) recognized alpha 150-169 and alpha 360-378. C57BL/6 mice recognized to a lesser extent also peptide alpha 181-200. In the present study we demonstrate that CD4+ cells which recognize these epitopes have T-helper function. CD4+ cells from TAChR immunized mice, stimulated in vitro with synthetic epitope peptides, induced proliferation in vitro of B cells via soluble factors which were not strain specific, and induced secretion in vitro of anti-AChR antibodies. Upon in vitro stimulation with T-epitope peptides, they secreted interleukin-2. Immunization of mice with synthetic T-epitope peptides caused sensitization of CD4+ cells, which responded in vitro both to the immunizing peptides and to TAChR, and appearance of anti-AChR antibodies in vivo, further identifying the epitope-specific CD4+ cells as AChR-specific T-helper cells.
Department of Biochemistry, University of Minnesota, St Paul 55108.
M
M
Bellone
N
N
Ostlie
S
S
Lei
A A
AA
Manfredi
B M
BM
Conti-Tronconi
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006239:Haplotypes; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009157:Myasthenia Gravis / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000302:isolation & purification; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014101:Torpedo
D000939:Epitopes; D006183:H-2 Antigens; D007376:Interleukin-2; D009842:Oligopeptides; D011950:Receptors, Cholinergic