Hypothetical three-dimensional structure of the TPO ectodomain based on the structure of myeloperoxidase (MPO). The ribbon diagram represents one TPO monomer beginning at residue 122 because no structural information is available on the N-terminal 121 amino acid prosequence of MPO (large blue circle), which is removed from the mature molecule. The C-terminus of MPO (“C578”) corresponds to TPO amino acid residue 736. Therefore, the diagram also does not provide insight into the region of the TPO ectodomain extending downstream to its insertion into the plasma membrane (residue 848). Epitopic footprinting identified lysine (K) 713 to be within the epitope of one of the human monoclonal TPO autoantibodies (TR1.9) that define the TPO immunodominant region. This residue is included in the linear epitope (shaded) of mouse mAb no. 47, which is recognized by a small proportion of TPO autoantibodies in an individual patient’s serum (16). Modified, with permission, from refs. 5, 19 (copyright 2001, The American Association of Immunologists).