Distinct genetic pattern of mouse susceptibility to thyroiditis induced by a novel thyroglobulin peptide.
Experimental autoimmune thyroiditis (EAT), induced by thyroglobulin (Tg) and adjuvant, is major histocompatibility complex-controlled and dependent on Tg-reactive T cells, but the immunopathogenic T-cell epitopes on Tg remain mostly undefined. We report here the thyroiditogenicity of a novel rat Tg peptide (TgP2; corresponding to human Tg amino acids 2695-2713), identified by algorithms as a site of putative T-cell epitope(s). TgP2 causes EAT in SJL (H-2s) but not in C3H or B10.BR (H-2k), BALB/c (H-2d), and B10 (H-2b) mice. This reveals a new genetic pattern of EAT susceptibility, since H-2k mice are known to be high responders (susceptible) after Tg challenge. Following in vivo priming with TgP2, T cells from only SJL mice proliferated significantly and consistently to TgP2 in vitro, whereas TgP2-specific IgG was observed in all strains tested. Adoptive transfer of TgP2-primed SJL lymph node cells to naive syngeneic recipients induced a pronounced mononuclear infiltration of the thyroid, which was more extensive than that observed after direct peptide challenge. TgP2 is non-immunodominant, since priming of SJL mice with rTg did not consistently elicit T-cell responses to TgP2 in vitro and a TgP2-specific T-cell hybridoma did not respond to antigen presenting cells pulsed with rTg. The data support the notion that Tg epitopes need not be either iodinated or immunodominant in order to cause severe thyroiditis and that the genetic pattern of the disease they induce can be distinct from that of Tg-mediated EAT.
Carayanniotis
G
G
Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Chronopoulou
E
E
Rao
V P
VP
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000276:immunology; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000737:chemistry / Q000276:immunology*; D013961:Thyroid Gland / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D006183:H-2 Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; C084243:thyroglobulin peptide (2695-2713); D013954:Thyroglobulin