Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation

Int Immunol. 2005 Dec;17(12):1607-17. doi: 10.1093/intimm/dxh340. Epub 2005 Nov 1.


The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8alpha and CD8beta levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells' ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Glycosylation
  • Histocompatibility Antigens Class I / immunology*
  • Ligands
  • Lymphocyte Activation / immunology*
  • Mice
  • Peptides / immunology
  • Protein Binding / immunology


  • CD8 Antigens
  • Histocompatibility Antigens Class I
  • Ligands
  • Peptides