Variable influences of iodine on the T-cell recognition of a single thyroglobulin epitope.
We have previously shown that iodotyrosyl formation within certain innocuous thyroglobulin (Tg) peptides confers on them immunopathogenic properties. In this report, we generated a panel of T-cell hybridoma clones specific for the immunogenic 16 mer Tg peptide p179 (amino acids 179-94) or its iodinated analogue (I-p179), with a view to examining the effects of a single iodine atom at the Y192 amino acid residue on T-cell recognition. We found that the peptide p179 was subdominant, and its binding to both A(k) and E(k) molecules was not significantly influenced by iodine. T-cell receptor (TCR) engagement was unaffected by the bulky iodine atom in two clones that responded to both analogues but it was sterically hindered in two other clones that recognized only p179. One clone was reactive only to I-p179, suggesting that the iodine atom is an integral part of its TCR ligand. Truncation analysis localized the determinant seen by all clones within the 11 mer peptide p184 (amino acids 184-194), suggesting that the cross-reactive clones were not activated by a minimal epitope lacking Y192 and that the negative influence of iodine was not the result of a flanking residue effect. These results demonstrate, at the clonal level, variable influences of a single iodine atom on the recognition of a single Tg peptide. Iodination of tyrosyl-containing, immunopathogenic Tg peptides may have unpredictable effects at the polyclonal level, depending on the extent of iodination at the particular site, and the relative number or effector function of autoreactive T-cell clones that are switched on or off by the neoantigenic determinant.
Jiang
Hong Y
HY
Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
Li
Haiyan S
HS
Carayanniotis
Karen
K
Carayanniotis
George
G
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007455:Iodine / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D013954:Thyroglobulin; D007455:Iodine