TCR signal transduction in antigen-specific memory CD8 T cells |
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Authors: | Kersh Ellen N Kaech Susan M Onami Thandi M Moran Miriana Wherry E John Miceli M Carrie Ahmed Rafi |
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Affiliation: | Department of Microbiology and Immunology, Emory Vaccine Center and Emory University School of Medicine, Atlanta, GA 30322, USA. |
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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. |
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