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Fine epitope mapping within the pathogenic thyroglobulin peptide 2340–2359: minimal epitopes retaining antigenicity across various MHC haplotypes are not necessarily immunogenic
Author(s) -
Hatzioannou Aikaterini,
Alevizaki Maria,
Carayanniotis George,
Lymberi Peggy
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03538.x
Subject(s) - epitope , biology , antigenicity , thyroglobulin , major histocompatibility complex , antigen , peptide , epitope mapping , amino acid , subdominant , peptide sequence , microbiology and biotechnology , genetics , antibody , biochemistry , gene
Summary 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.