Differential SLP-76 expression and TCR-mediated signaling in effector and memory CD4 T cells.
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.
Hussain
S Farzana
SF
Department of Surgery, University of Maryland, Baltimore, MD 21201, USA.
Anderson
Charles F
CF
Farber
Donna L
DL
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D051380:GRB2 Adaptor Protein; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins