Cellular thyroid peroxidase (TPO), unlike purified TPO and adjuvant, induces antibodies in mice that resemble autoantibodies in human autoimmune thyroid disease

Autoantibodies to several protein antigens in human autoimmunity interact w ith a restricted range of epitopes, whereas diverse epitopes are recognized by antibodies induced in animals using antigen and adjuvant. To examine th e basis for this difference, we compared the qualitative nature of antibodi es developing in AKR/N mice injected with purified thyroid peroxidase (TPO) and adjuvant or with TPO expressed on major histocompatibility complex (NM C) class II+ fibroblasts. Mice injected with purified TPO had higher TPO an tibody levels than TPO+/class II+ fibroblast-treated mice. Despite lower ti ters, recipients of TPO+/class II+ cells developed very high affinity antib odies (K-d = similar to 10(-10) M), comparable with those of human TPO auto antibodies and about 10-fold higher than those in purified TPO plus adjuvan t-immunized mice, Moreover, more than 90% of TPO antibodies in TPO+/class I I+ fibroblast-injected mice, compared with only approximately 50% in TPO pl us adjuvant-immunized mice, were to the immunodominant region recognized by patients' autoantibodies. Consistent with this epitopic restriction, TPO+/ class II+ fibroblast-injected mice had TPO antibody epitopic fingerprints s imilar to those of human autoantibodies. In conclusion, mice injected with TPO+/class II+ fibroblasts, but not those injected with purified TPO and adjuvant, develop antibodies closely resemb ling autoantibodies in human disease. These observations indicate that some animal models based on conventional immunization may not be representative of human diseases with a major humoral component.