An endogenous peptide positively selects and augments the activation and survival of peripheral CD4+ T cells

Nat Immunol. 2009 Nov;10(11):1155-61. doi: 10.1038/ni.1796. Epub 2009 Oct 4.


Although CD4(+) and CD8(+) T cells differ in the strength of their positively selecting signal, endogenous positively selecting ligands have been identified only for major histocompatibility complex (MHC) class I-restricted T cell antigen receptors (TCRs). Here we screened for ligands able to positively select MHC class II-restricted TCRs using thymocytes from four I-E(k)-restricted TCR-transgenic mice and a large panel of self peptides. One peptide, gp250, induced positive selection of AND CD4(+) T cells, had no homology with the AND TCR agonist ligand and was recognized with a high degree of specificity. The gp250 peptide acted as a coagonist to initiate the activation and enhance the survival of peripheral AND CD4(+) T cells. Thus, positively selecting ligands are critical in thymocyte development and in the activation and maintenance of peripheral T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cell Proliferation
  • Histocompatibility Antigens Class II / immunology*
  • Lectins, C-Type
  • Ligands
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Peptides / immunology*
  • Protein Binding
  • Receptors, Antigen, T-Cell / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Histocompatibility Antigens Class II
  • Lectins, C-Type
  • Ligands
  • Peptides
  • Receptors, Antigen, T-Cell