Thyroxine-binding antibodies inhibit T cell recognition of a pathogenic thyroglobulin epitope.
Thyroid hormone-binding (THB) Abs are frequently detected in autoimmune thyroid disorders but it is unknown whether they can exert immunoregulatory effects. We report that a THB mAb recognizing the 5' iodine atom of the outer phenolic ring of thyroxine (T4) can block T cell recognition of the pathogenic thyroglobulin (Tg) peptide (2549-2560) that contains T4 at aa position 2553 (T4(2553)). Following peptide binding to the MHC groove, the THB mAb inhibited activation of the A(k)-restricted, T4(2553)-specific, mouse T cell hybridoma clone 3.47, which does not recognize other T4-containing epitopes or noniodinated peptide analogues. Addition of the same THB mAb to T4(2553)-pulsed splenocytes largely inhibited specific activation of T4(2553)-primed lymph node cells and significantly reduced their capacity to adoptively transfer thyroiditis to naive CBA/J mice. These data demonstrate that some THB Abs can block recognition of iodine-containing Tg epitopes by autoaggressive T cells and support the view that such Abs may influence the development or maintenance of thyroid disease.
Dai
Yang D
YD
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Eliades
Petros
P
Carayanniotis
Karen A
KA
McCormick
Daniel J
DJ
Kong
Yi-Chi M
YC
Magafa
Vassiliki
V
Cordopatis
Paul
P
Lymberi
Peggy
P
Carayanniotis
George
G
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D017951:Antigen Presentation / Q000276:immunology*; D001323:Autoantibodies / Q000378:metabolism* / Q000502:physiology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D045744:Cell Line, Tumor; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D007455:Iodine / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000517:prevention & control; D013974:Thyroxine / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D013954:Thyroglobulin; D007455:Iodine; D013974:Thyroxine
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