Unique role of thyroxine in T cell recognition of a pathogenic peptide in experimental autoimmune thyroiditis.
We have previously demonstrated the importance of iodination and the requirement of the thyroxine residues in thyroglobulin (Tg) for the stimulation of two clonotypically distinct murine T cell hybridomas reactive against human and mouse Tg. We are now able to show that these T cell hybridomas only recognize an 11-residue peptide containing a thyroxine structure that has iodine at two positions on each ring. This iodination state is critical for recognition by these hybridomas as a peptide containing de-iodinated thyroxine is nonstimulatory. Furthermore we have demonstrated that a peptide lacking the thyroxine residue or containing de-iodinated thyroxine cannot block the recognition of the thyroxine-containing peptide. We suggest that in our system the thyroxine residue is involved in binding to major histocompatibility complex (MHC) class II molecules. We have also been able to show that the thyroxine residue is available for contact by the T cell receptor (TCR) as recognition of the peptide/H-2A(k) complex is blockable by an antibody directed against thyroxine. Using substituted peptides, we have been able partially to define the residues within the peptide that are critical for recognition of the 11-residue peptide by our hybridomas. From our data, we suggest that the thyroxine residue may bind the MHC and TCR, while the residues identified in the peptide backbone as important for the stimulation of the hybridomas may bind only the TCR.
Dawe
K I
KI
Department of Immunology, ASH, UCMSM, London, GB.
Hutchings
P R
PR
Geysen
M
M
Champion
B R
BR
Cooke
A
A
Roitt
I M
IM
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D000939:Epitopes; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007111:Immunity, Cellular; D007455:Iodine / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013954:Thyroglobulin / Q000737:chemistry / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000503:physiopathology*; D013974:Thyroxine / Q000502:physiology*
D000939:Epitopes; D010446:Peptide Fragments; D013954:Thyroglobulin; D007455:Iodine; D013974:Thyroxine