Activated Antigen-Presenting Cells Select and Present Chemically Modified Peptides Recognized by Unique CD4 T Cells

Proc Natl Acad Sci U S A. 2005 May 31;102(22):7928-33. doi: 10.1073/pnas.0502255102. Epub 2005 May 18.

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-A(k). 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigen Presentation / immunology*
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Listeria monocytogenes
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • Muramidase / immunology
  • Muramidase / metabolism*

Substances

  • Antibodies, Monoclonal
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • hen egg lysozyme
  • Muramidase