Original Article

T Cell Recognition of the Dominant I-A^k–restricted Hen Egg Lysozyme Epitope: Critical Role for Asparagine Deamidation

Correspondence to: Stephen N. McAdam, Institute of Immunology, University of Oslo, Rikshospitalet, Oslo N-0027, Norway. Tel:47-2307-1374 Fax:47-2307-3510 E-mail:stephen.mcadam{at}labmed.uio.no.

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.

Key Words: posttranslational/chemical modification, autoimmunity, peptide, deamidation, T cell

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