title: Thyroxine-binding antibodies inhibit T cell recognition of a pathogenic thyroglobulin epitope.
abstract: 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.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Yang D
authors.initials: YD
authors.lastname: Dai
authors.forename: Petros
authors.initials: P
authors.lastname: Eliades
authors.forename: Karen A
authors.initials: KA
authors.lastname: Carayanniotis
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McCormick
authors.forename: Yi-Chi M
authors.initials: YC
authors.lastname: Kong
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Magafa
authors.forename: Paul
authors.initials: P
authors.lastname: Cordopatis
authors.forename: Peggy
authors.initials: P
authors.lastname: Lymberi
authors.forename: George
authors.initials: G
authors.lastname: Carayanniotis
mesh_terms: 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
chemical_list: 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
references.citation: Int Rev Immunol. 2000;19(6):557-72
references.pmid: 11129115
references.citation: J Immunol. 2002 Jun 1;168(11):5907-11
references.pmid: 12023396
references.citation: J Immunol. 2002 Nov 1;169(9):5332-7
references.pmid: 12391254
references.citation: Thyroid. 2003 Feb;13(2):211-5
references.pmid: 12699597
references.citation: J Endocrinol Invest. 2003 Apr;26(4):294-300
references.pmid: 12841535
references.citation: Autoimmunity. 2003 Sep-Nov;36(6-7):423-8
references.pmid: 14669951
references.citation: J Immunol. 1971 Oct;107(4):997-1003
references.pmid: 4106097
references.citation: J Immunol. 1983 May;130(5):2287-94
references.pmid: 6300242
references.citation: Surv Immunol Res. 1983;2(3):223-9
references.pmid: 6201979
references.citation: Biochem J. 1984 Apr 15;219(2):405-10
references.pmid: 6743226
references.citation: J Immunol. 1985 Jun;134(6):3845-8
references.pmid: 3989298
references.citation: Immunol Invest. 1986 Aug;15(5):481-92
references.pmid: 3096882
references.citation: Endocrinology. 1987 May;120(5):2078-84
references.pmid: 3569125
references.citation: J Immunol. 1987 Jun 15;138(12):4133-42
references.pmid: 2438335
references.citation: J Immunol. 1987 Dec 1;139(11):3665-70
references.pmid: 2445818
references.citation: J Endocrinol Invest. 1987 Dec;10(6):605-19
references.pmid: 3326894
references.citation: Mol Cell Endocrinol. 1988 Jun;57(3):261-7
references.pmid: 3402664
references.citation: J Biol Chem. 1989 Aug 15;264(23):13541-5
references.pmid: 2760035
references.citation: J Immunol. 1991 Apr 1;146(7):2137-44
references.pmid: 1706388
references.citation: Nature. 1991 May 9;351(6322):147-50
references.pmid: 1709449
references.citation: J Exp Med. 1991 Jul 1;174(1):243-51
references.pmid: 2056278
references.citation: J Exp Med. 1991 Aug 1;174(2):363-70
references.pmid: 1713250
references.citation: Mol Cell Endocrinol. 1991 Aug;79(1-3):93-8
references.pmid: 1936549
references.citation: J Exp Med. 1992 Mar 1;175(3):869-72
references.pmid: 1740668
references.citation: J Immunol. 1992 Jun 1;148(11):3483-91
references.pmid: 1375245
references.citation: J Immunol. 1992 Aug 1;149(3):1039-44
references.pmid: 1378862
references.citation: J Clin Lab Immunol. 1991 Sep;36(1):33-8
references.pmid: 1668859
references.citation: Immunogenetics. 1994;39(1):21-8
references.pmid: 8225435
references.citation: Clin Chem. 1995 Jan;41(1):117-8
references.pmid: 7813060
references.citation: Crit Rev Immunol. 1994;14(2):157-91
references.pmid: 7535535
references.citation: J Immunol. 1995 Dec 15;155(12):5847-54
references.pmid: 7499874
references.citation: Eur J Immunol. 1996 Apr;26(4):768-72
references.pmid: 8625966
references.citation: Clin Immunol Immunopathol. 1998 Jan;86(1):110-4
references.pmid: 9434803
references.citation: J Autoimmun. 1997 Dec;10(6):531-40
references.pmid: 9451592
references.citation: Clin Chem. 1998 Mar;44(3):440-54
references.pmid: 9510847
references.citation: J Immunol. 1998 Jul 15;161(2):767-75
references.pmid: 9670953
references.citation: J Immunol. 1999 May 15;162(10):5888-93
references.pmid: 10229824
references.citation: J Immunol. 1999 Jun 15;162(12):6987-92
references.pmid: 10358139