[Autoimmune response to thyroglobulin. Proliferative response to thyroglobulin fragments in low responder mice]

Thyroglobulin (Tg) is one of the major thyroid autoantigens involved in autoimmune thyroiditis. The immune response of mice to Tg is genetically controlled by H-2-linked genes. To elucidate the regulation mechanism of autoimmune response to Tg in low responder mice, we studied the proliferative response of lymph node cells (LNC) to mouse Tg (MTg) and enzyme-digested MTg fragments. MTg was treated with Staphylococcus aureus V8 protease followed by separation of the fragments into 6 fractions (Fr1-Fr6: 264,000-17,000) by high performance liquid chromatography (HPLC), LNC from MTg immunized CBA/N (H-2k) mice, a high responder strain, proliferated in response to MTg and all fractions (Fr1-Fr6) of MTg fragments in vitro. In contrast, LNC from MTg immunized BALB/c (H-2d) and B10 (H-2b) mice, low responder strains, did not respond to native Tg but responded well to some smaller Tg fractions (Fr3, 4, 5). In addition, when BALB/c mice were immunized with MTg Fr4 with a molecular weight of 63,000, LNC from BALB/c mice proliferated in response to MTg as well as MTg Fr4. These findings suggest that T cells which are capable of responding to Tg do exist even in low responder mice and that the activation of these autoreactive T cells is suppressed by a regulatory cell subpopulation in low responder mice.