Does the autoantibody immunodominant region on thyroid peroxidase include amino acid residues 742-771?

Identification of the thyroid peroxidase (TPO) amino acid residues that com prise the autoantibody immunodominant region is an important goal that has proven difficult because of the conformational nature of the epitopes invol ved. Recent data suggest that the immunodominant region has been located. T hus, by autoantibody recognition of tryptic fragments of native TPO, as wel l as of conformational portions of TPO expressed as cell-free translates, t he autoantibody immunodominant region appears to include amino acid residue s 742-771, near the C terminus of the ectodomain. To evaluate this deductio n, we expressed as cell-free translates the full TPO ectodomain, as well as TPO truncated after residues 741 and 771. The epitopic integrity of these molecules was first confirmed by immunoprecipitation by patient sera contai ning TPO autoantibodies. However, autoantibody recognition could involve a minority of TPO autoantibodies with the individual sera, not fulfilling the strict criteria for immunodominance. In order to obtain definitive data, w e performed immunoprecipitations on these TPO variants with four recombinan t human monoclonal autoantibodies that define the immunodominant region. Al l four monoclonal autoantibodies immunoprecipitated TPO 1-741 to the same e xtent as they did TPO 1-771 and the full TPO ectodomain, indicating that th e immunodominant region comprises (at least in large part) amino acid resid ues upstream of residue 741.