Thyroxine-Binding Antibodies Inhibit T Cell Recognition of a Pathogenic Thyroglobulin Epitope

• Published in: The Journal of immunology (1950) Vol. 174; no. 5; pp. 3105 - 3110
• Main Authors: Dai, Yang D, Eliades, Petros, Carayanniotis, Karen A, McCormick, Daniel J, Kong, Yi-chi M, Magafa, Vassiliki, Cordopatis, Paul, Lymberi, Peggy, Carayanniotis, George
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-03-2005
• Subjects: Adoptive Transfer; Animals; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; Antibody Specificity; Antigen Presentation - immunology; Autoantibodies - metabolism; Autoantibodies - physiology; Binding Sites, Antibody; Binding, Competitive - immunology; Cell Line, Tumor; Clone Cells; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; Female; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Hybridomas; Iodine - metabolism; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Peptide Fragments - immunology; Peptide Fragments - metabolism; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - physiology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thyroglobulin - immunology; Thyroiditis, Autoimmune - immunology; Thyroiditis, Autoimmune - prevention & control; Thyroxine - chemistry; Thyroxine - immunology; Thyroxine - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.5.3105

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.