Weak agonist self-peptides promote selection and tuning of virus-specific T cells

Eur J Immunol. 2003 Mar;33(3):685-96. doi: 10.1002/eji.200323143.


Recent progress has begun to define the interactions and signaling pathways that are triggered during positive selection. To identify and further examine self-peptides that can mediate positive selection, we searched a protein-database to find peptides that have minimal homology with the viral peptide (p33) that activates a defined P14 transgenic TCR. We identified four peptides that could bind the restriction element H-2D(b) and induce proliferation of P14 transgenic splenocytes at high concentration. Two of the four peptides (DBM and RPP) were able to positively select the virus-specific TCR in fetal thymic organ culture but were unable to induce clonal deletion. Reverse-phase HPLC and mass spectrometry demonstrated that these peptides were presented by H-2D(b) molecules on thymic epithelial cell lines. We also examined whether the selecting ligands altered T cell responsiveness in vitro. DBM-selected T cells lost their ability to respond to the positively selecting ligand DBM, whereas RPP-selected T cells only retained their ability to respond to high concentrations of RPP. These results demonstrate that self-peptides that mediate positive selection can differentially "tune" the activation threshold of T cells and alter the functional repertoire of T cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dopamine beta-Hydroxylase / immunology
  • ErbB Receptors / immunology
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Lymphocyte Activation*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Receptors, Antigen, T-Cell / physiology*
  • T-Lymphocytes / immunology*


  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Dopamine beta-Hydroxylase
  • ErbB Receptors