TCR signal transduction in antigen-specific memory CD8 T cells

• Published in: The Journal of immunology (1950) Vol. 170; no. 11; pp. 5455 - 5463
• Main Authors: Kersh, Ellen N, Kaech, Susan M, Onami, Thandi M, Moran, Miriana, Wherry, E John, Miceli, M Carrie, Ahmed, Rafi
• Format: Journal Article
• Language: English
• Published: United States 01.06.2003
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• 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.