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Introduction ‐ The presence of T‐cell reactivity to αB‐crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS. Material and methods ‐ We have tested the serum of patients with clinically definite MS (n= 30), other inflammatory neurological disease (n= 22), non‐inflammatory neurological disease (n= 42) and healthy individuals (n= 23) for systemic humoral responses to bovine αB‐crystallin, to the homologous chaperone protein, αA‐crystallin, and to another small Hsp, Hsp 27. Results ‐ Sixty‐three percent of MS patients exhibited immunoreactivity to α‐crystallin and this was present in all 4 of 4 non‐ambulatory patients with MS. In contrast, serum concentrations in MS patients of antibodies to the small Hsp, Hsp27, and to myelin basic protein were negligible (P<0.001). Serum anti‐α‐crystallin immune responses were detected in significantly lower percentages of patients with other inflammatory neurological diseases (32%, P<0.025), and with non‐inflammatory neurological diseases (12%, P<0.001). None of the healthy control individuals showed anti‐α‐crystallin reactivity. The concentration of anti‐α‐crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025). Conclusion ‐ Our observations support the notion that anti‐α‐crystallin autoimmune responses may contribute to pathogenicity in MS and may represent a mechanism of how recurrent attacks of MS develop subsequent to an isolated demyelinating episode.

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Anti-acetylcholine receptor (AChR) monoclonal antibody 383C binds to the beta-hairpin loop alpha(187-199) of only one of the two Torpedo AChR alpha subunits. The loop recognized is associated with the alpha subunit corresponding to the high-affinity d-tubocurarine (dTC) binding site. Desensitization of the receptor with carbamylcholine completely blocks the binding of 383C. Mild reduction of AChR alpha subunit cys 192-193 disulfide with DTT and subsequent reaction with 5-iodoacetamidofluorescein label only the high-affinity dTC alpha subunit. Rhodamine-labeled alpha-bungarotoxin (R-Btx) binds to the unlabeled AChR alpha subunit as monitored by fluorescence resonance energy transfer between the fluorescein and rhodamine dyes. A 10-A contraction of the distance between the dyes is observed following the addition of carbamylcholine. In a small angle X-ray diffraction experiment exploiting anomalous X-ray scattering from Tb(III) ions titrated into AChR Ca(II) binding sites, we find evidence for a change in the Tb(III) ion distribution in the region of the ion channel following addition of carbamylcholine to the AChR. The carbamylcholine-induced loss of the 383C epitope, the 10-A contraction of the beta-hairpin loop, and the loss of multivalent cations from the channel likely represent the first molecular transitions leading to AChR channel opening.

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