In vitro and in vivo autoimmune response to enamel matrix proteins

Enamel matrix proteins taken from neonatal C57Bl/6 mice were shown to be able to elicit in vitro proliferative responses in C57Bl/6 splenic lymphocytes taken from animals which had not been exposed to exogenous enamel proteins. Animals which had been injected with enamel matrix proteins in Freund's complete adjuvant made IgG antibodies against enamel proteins which were detected by indirect immunofluorescence. Spleen cells from the immune animals gave an augmented in vitro proliferative response to enamel proteins, while spleen cells from C57Bl/6 nu/nu mice or anti-Thy 1 and complement-treated normal C57Bl/6 spleen cells were incapable of responding to enamel proteins in vitro. Thus, enamel matrix proteins appear to be T-cell dependent autoantigens. The natural history of enamel matrix proteins is reviewed, and it is suggested, based on the anatomic details of enamel synthesis, secretion, and maturation, that enamel matrix proteins are autoantigenic because they are anatomically sequestered.