E. Chronopoulou et al., AUTOREACTIVE IGG ELICITED IN MICE BY THE NONDOMINANT BUT PATHOGENIC THYROGLOBULIN PEPTIDE-(2495-2511) - IMPLICATIONS FOR THYROID AUTOIMMUNITY, Clinical and experimental immunology, 98(1), 1994, pp. 89-94
We have previously shown that mice challenged with the rat thyroglobul
in (Tg) peptide TgP1 (corresponding to aa 2495-2511 of human Tg) devel
op experimental autoimmune thyroiditis (EAT) and produce IgG antibodie
s that cross-react with Tg from various species. It was not clear, how
ever, whether such antibodies were TgP1-specific or were induced secon
darily-i.e. by autologous Tg released from the destroyed gland-and the
refore directed to determinants other than TgP1. In this study we desc
ribe that, 5 weeks after priming with TgP1, the binding of serum IgG o
n native Tg is completely inhibited by free peptide, suggesting lack o
f recognition of other determinants on mouse Tg (mTg). In addition, Tg
P1-induced but not mTg-induced IgG bound better to heat-denatured than
intact mTg, a result compatible with the recognition of a linear epit
ope by the peptide-induced antibodies. Comparison of the IgG subclass
distribution among mTg-induced versus TgP1-induced IgG did not reveal
qualitative differences, since all subclasses were represented in the
order IgG1 > IgG2b > IgG2a > IgG3. Finally, TgP1-specific IgG reacted
strongly with the follicular colloid in sections of normal thyroids, i
ndicating the potential to bind to native Tg in vivo. These data: (i)
highlight TgP1 as the only, so far, Tg sequence known to generate both
EAT and Tg-reactive IgG in mice; and (ii) do not provide evidence for
an amplification of the Tg-specific IgG response through the involvem
ent of endogenous autoantigen in EAT.