[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].
There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.
Hoshioka
A
A
Department of Pediatrics, School of Medicine, Chiba University.
Kohno
Y
Y
Katsuki
T
T
Shimojo
N
N
Sakata
S
S
Inagaki
Y
Y
Maruyama
N
N
Tarutani
O
O
Yokochi
T
T
Niimi
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D013954:Thyroglobulin / Q000276:immunology* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D014443:Tyrosine; D013954:Thyroglobulin; D007455:Iodine