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)¹ α subunit recognized by CD4⁺ cells of congenic mouse strains of different H-2 haplotypes, susceptible to experimental auto-immune myasthenia gravis. CD4⁺ cells from BALB/c and CB17 mice (H-2^d) recognized the peptide sequences α1-20 and α304-322, while C57BL/6 and BALB/b mice (H-2^b) recognized α150-169 and α360-378. C57Bl/6 mice recognized to a lesser extent also peptide α181-200. 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.