Differential SLP-76 Expression and TCR-Mediated Signaling in Effector and Memory CD4 T Cells

• Published in: The Journal of immunology (1950) Vol. 168; no. 4; pp. 1557 - 1565
• Main Authors: Hussain, S. Farzana, Anderson, Charles F, Farber, Donna L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2002
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Blotting, Western; CD4-Positive T-Lymphocytes - immunology; Cells, Cultured; GRB2 Adaptor Protein; Immunologic Memory; Lymphocyte Activation; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Models, Immunological; Phosphoproteins - metabolism; Phosphorylation; Precipitin Tests; Proteins - metabolism; Receptors, Antigen, T-Cell - metabolism; SLP-76 protein; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.4.1557

We present in this study novel findings on TCR-mediated signaling in naive, effector, and memory CD4 T cells that identify critical biochemical markers to distinguish these subsets. We demonstrate that relative to naive CD4 T cells, memory CD4 T cells exhibit a profound decrease in expression of the linker/adapter molecule SLP-76, while effector T cells express normal to elevated levels of SLP-76. The reduced level of SLP-76 is memory CD4 T cells is coincident with reduced phosphorylation overall, yet the residual SLP-76 couples to a subset of TCR-associated linker molecules, leading to downstream mitogen-activated protein (MAP) kinase activation. By contrast, effector CD4 T cells strongly phosphorylate SLP-76, linker for activation of T cells, and additional Grb2-coupled proteins, exhibit increased associations of SLP-76 to phosphorylated linkers, and hyperphosphorylate downstream Erk1/2 MAP kinases. Our results suggest distinct coupling of signaling intermediates to the TCR in naive, effector, and memory CD4 T cells. Whereas effector CD4 T cells amplify existing TCR signaling events accounting for rapid effector responses, memory T cells engage fewer signaling intermediates to efficiently link TCR triggering directly to downstream MAP kinase activation.