CD8 expression allows T cell signaling by monomeric peptide-MHC complexes

Immunity. 1998 Oct;9(4):467-73. doi: 10.1016/s1074-7613(00)80630-5.


Physiologically, TCR signaling is unlikely to result from the cross-linking of TCR-CD3 complexes, given the low density of specific peptide-MHC complexes on antigen-presenting cells. We therefore have tested directly an alternative model for antigen recognition. We show that monomers of soluble peptide-MHC trigger Ca2+ responses in CD8alphabeta+ T cells. This response is not observed in CD8- T cells and when either the CD8:MHC or CD8:Lck interactions are prevented. This demonstrates that an intact CD8 coreceptor is necessary for effective TCR signaling in response to monomeric peptide-MHC molecules. We propose that this heterodimerization of TCR and CD8 by peptide-MHC corresponds to the physiological event normally involved during antigen-specific signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8 Antigens / chemistry
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Calcium Signaling
  • Dimerization
  • Histocompatibility Antigens / metabolism
  • Hybridomas / immunology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Mice
  • Mice, Transgenic
  • Peptides / genetics
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / immunology*
  • Transfection


  • CD8 Antigens
  • Histocompatibility Antigens
  • Peptides
  • Receptors, Antigen, T-Cell
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)