TCR signal transduction in antigen-specific memory CD8 T cells

J Immunol. 2003 Jun 1;170(11):5455-63. doi: 10.4049/jimmunol.170.11.5455.


Memory T cells are more responsive to Ag than naive cells. To determine whether memory T cells also have more efficient TCR signaling, we compared naive, effector, and memory CD8 T cells of the same antigenic specificity. Surprisingly, initial CD3 signaling events are indistinguishable. However, memory T cells have more extensive lipid rafts with higher phosphoprotein content before TCR engagement. Upon activation in vivo, they more efficiently induce phosphorylation of-LAT (linker for activation of T cells), ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38. Thus, memory CD8 T cells do not increase their TCR sensitivity, but are better poised to augment downstream signals. We propose that this regulatory mechanism might increase signal transduction in memory T cells, while limiting TCR cross-reactivity and autoimmunity.

Publication types

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

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Separation
  • Epitopes, T-Lymphocyte / physiology*
  • Immunologic Memory* / genetics
  • Interphase / genetics
  • Interphase / immunology
  • Lymphocyte Activation / genetics
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Up-Regulation / genetics
  • Up-Regulation / immunology
  • ZAP-70 Protein-Tyrosine Kinase


  • CD3 Complex
  • CD3 antigen, zeta chain
  • Epitopes, T-Lymphocyte
  • Phosphoproteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse