title: Fine epitope mapping within the pathogenic thyroglobulin peptide 2340-2359: minimal epitopes retaining antigenicity across various MHC haplotypes are not necessarily immunogenic.
abstract: We have previously reported that the 20-mer peptide p2340 (amino acids 2340-2359), of human thyroglobulin (Tg) has the unique feature that it causes experimental autoimmune thyroiditis (EAT) in mouse strains bearing high-responder (HR) or low-responder (LR) MHC haplotypes in Tg-induced EAT. In this study, we have employed fine epitope mapping to examine whether this property of p2340 is the result of recognition of distinct or shared minimal T-cell epitopes in the context of HR or LR MHC class II molecules. Use of overlapping peptides showed that a core minimal 9-mer epitope (LTWVQTHIR, amino acids 2344-2352) was recognized by p2340-primed T cells from both HR (H2(k,s) ) and LR (H2(b,d) ) strains, whereas a second 9-mer epitope (HIRGFGGDP, amino acids 2350-2358) was antigenic only in H2(s)  hosts. Truncation analysis of LTWVQTHIR and HIRGFGGDP peptides delineated them as the minimal epitopes recognized by p2340-primed T cells from the above strains. Subcutaneous challenge of all mouse strains with the 9-mer core peptide LTWVQTHIR in adjuvant elicited specific lymph node cell proliferative responses and mild EAT only in HR hosts, highlighting this sequence as a minimal pathogenic Tg peptide in EAT. The 9-mer peptide HIRGFGGDP was not found to be immunogenic in H2(s)  hosts. These data demonstrate that minimal T-cell epitopes, defined as autoantigenic in hosts of various MHC haplotypes, are not intrinsically immunogenic. Activation of naive autoreactive T cells may require contributions from flanking residues within longer peptide sequences encompassing these epitopes.
authors.affiliation: Immunology Laboratory, Biochemistry Department, Hellenic Pasteur Institute, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Hatzioannou
authors.forename: Maria
authors.initials: M
authors.lastname: Alevizaki
authors.forename: George
authors.initials: G
authors.lastname: Carayanniotis
authors.forename: Peggy
authors.initials: P
authors.lastname: Lymberi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D018604:Epitope Mapping; D005260:Female; D006183:H-2 Antigens; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology
chemical_list: D001324:Autoantigens; D006183:H-2 Antigens; D010446:Peptide Fragments; D013954:Thyroglobulin
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