Thyrotropin stimulates specifically the expression of the autoantibody binding domains of the thyroperoxidase molecule.
To get some insight on the in vitro effect of TSH on the expression of two thyroid specific antigens (thyroglobulin (Tg) and thyroid peroxidase (TPO)) on the cell surface of cultured human thyroid cells an indirect immunofluorescence-activated cell sorter (FACStar IV, Becton-Dickinson) was used. Only half of the cultures responded to TSH by increased surface expression of the thyroid specific antigen Tg. In these cells, TSH stimulation of TPO expression showed a difference in epitopes recognized by murine monoclonal antibodies. Epitopes of domain D, recognized by monoclonal antibody 1, 30, 40 and 53 which are not involved in autoimmunity, were unaffected by TSH stimulation, (n = 2-10). In contrast, TSH regulated the surface expression of the TPO epitopes recognized by monoclonal antibody 15, 18, 24 and 60, which are known to be related to the serum autoantibody binding domain of TPO, (n = 6-8; p < 0.05). This indicated that increased activity of the thyroid cells selectively stimulated the expression of autoantigenic epitopes on the cell surface and supports the concept that increased cellular activity might predispose to the autoimmune processes leading to autoimmune thyroid disease.
Rasmussen
A K
AK
Department of Endocrinology P2131, National University Hospital, Copenhagen, Denmark.
Feldt-Rasmussen
U
U
Brandt
M
M
Hartoft-Nielsen
M L
ML
Carayon
P
P
Buschard
K
K
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology*; D051379:Mice; D013961:Thyroid Gland / Q000201:enzymology / Q000276:immunology; D013972:Thyrotropin / Q000276:immunology*
D001323:Autoantibodies; D016056:Immunodominant Epitopes; D013972:Thyrotropin; D007453:Iodide Peroxidase