Activated antigen-presenting cells select and present chemically modified peptides recognized by unique CD4 T cells

Jeremy Herzog, Yoichi Maekawa, Thomas P. Cirrito, Beverly S. Illian, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

CD4 T cells recognized posttranslationally modified peptides of the protein hen egg-white lysozyme (HEL), consisting of nitration of tyrosines and modifications of tryptophans in the T cell contact residues of the peptides. T cells were directed against modifications of a chemically dominant HEL peptide as well as a minor HEL peptide, bound to the class II histocompatibility molecule I-Ak. The modified peptides were generated in vivo after immunization with native HEL molecules or were generated ex vivo by peroxynitrite treatment of HEL. Moreover, antigen-presenting cells (APC), either macrophages or dendritic cells activated in culture or in vivo, generated the modified HEL epitopes that stimulated the T cells. In transgenic mice expressing HEL, the T cells to the modified epitopes escaped negative selection and were found, albeit fewer in number than in normal mice. Infection with Listeria monocytogenes of the transgenic HEL mice generated APC containing the modifications. T cells to modified epitopes induced by activation of APC may be a component of antimicrobial immunity and autoimmune reactions.

Original languageEnglish
Pages (from-to)7928-7933
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number22
DOIs
StatePublished - May 31 2005

Keywords

  • Histocompatability molecules
  • Nitrotyrosine
  • Posttranslational modification

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