Low-avidity recognition by CD4+ T cells directed to self-antigens

Eur J Immunol. 2003 May;33(5):1409-17. doi: 10.1002/eji.200323871.


Self-reactive T cells populate the peripheral immune system, and likely form the reservoir from which autoreactive cells are derived. We analyzed a panel of self and non-self peptides presented by HLA-DR4, a class II molecule associated with autoimmunity, by immunization of mice transgenic for HLA-DR4. Significant structural avidity for T cell recognition, as measured by MHC class II tetramer binding to CD4(+) T cells was only observed in mice immunized with the non-self antigens. T cell hybridomas were generated from mice immunized with the naturally processed self-peptide hGAD65 (552-572) and also from mice immunized with an influenza-derived non-self epitope (HA 306-318). T cells specific for the self peptide failed to bind tetramers and exhibited low functional avidity as measured by the peptide concentration required to reach half-maximum proliferation values. In contrast, T cells specific for the non-self HA (306-318) peptide exhibited high structural and functional avidity profiles. As recently described in studies of murine CD8(+) T cell function, the predominance of low avidity recognition of self-peptide epitopes may be a characteristic feature of CD4(+) T cells responding to autoantigens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Glutamate Decarboxylase / immunology
  • HLA-DR4 Antigen / chemistry
  • HLA-DR4 Antigen / metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Hybridomas / immunology
  • Immunization
  • Isoenzymes / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / analysis


  • Autoantigens
  • HLA-DR4 Antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Isoenzymes
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2