Abstract
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
Substances
-
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