T Cell Recognition of the Dominant I-Ak–Restricted Hen Egg Lysozyme Epitope Critical Role for Asparagine Deamidation

Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL 48–62 ) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-A k in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL pe...

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Published inThe Journal of experimental medicine Vol. 193; no. 11; pp. 1239 - 1246
Main Authors McAdam, Stephen N., Fleckenstein, Burkhard, Rasmussen, Ingunn B., Schmid, Dietmar G., Sandlie, Inger, Bogen, Bjarne, Viner, Nicholas J., Sollid, Ludvig M.
Format Journal Article
LanguageEnglish
Published The Rockefeller University Press 04.06.2001
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Summary:Type-B T cells raised against the immunodominant peptide in hen egg lysozyme (HEL 48–62 ) do not respond to whole lysozyme, and this has been thought to indicate that peptide can bind to l-A k in different conformations. Here we demonstrate that such T cells recognize a deamidated form of the HEL peptide and not the native peptide. The sequence of the HEL epitope facilitates rapid and spontaneous deamidation when present as a free peptide or within a flexible domain. However, this deamidated epitope is not created within intact lysozyme, most likely because it resides in a highly structured part of the protein. These findings argue against the existence of multiple conformations of the same peptide–MHC complex and have important implications for the design of peptide-based vaccines. Furthermore, as the type-B T cells are known to selectively evade induction of tolerance when HEL is expressed as a transgene, these results suggest that recognition of posttranslationally modified self-antigen may play a role in autoimmunity.
ISSN:0022-1007
1540-9538