Acetylcholine receptor-reactive T lymphocytes from healthy subjects and myasthenia gravis patients

Abstract

Peripheral blood lymphocytes from 23 of 114 (20%) myasthenia gravis (MG) patients showed positive T-cell proliferative responses to native acetylcholine receptor (AChR) purified from the electric fish Torpedo, compared with two of 25 (8%) healthy or other neurologic disease controls. Responsiveness appeared to fluctuate seasonally. Long-term T-cell lines and clones could be selected as readily from the two healthy responders as from the MG cases and showed similar culture behavior, CD4+ phenotype, and HLA class II restrictions. One clone from a control cross-reacted with recombinant human AChR alpha chain (r37-429A) and with the synthetic peptide 125-143(S-S) from its sequence. Both these human antigens stimulated primary proliferative responses at substantially higher frequencies (26 to 59%) than native xeno-AChR--in both patients and controls--demonstrating that truly autoreactive T cells are not inevitably deleted during normal T-cell development.