The FcR gamma subunit and Syk kinase replace the CD3 zeta-chain and ZAP-70 kinase in the TCR signaling complex of human effector CD4 T cells.
The TCR-mediated signals required to activate resting T cells have been well characterized; however, it is not known how TCR-coupled signals are transduced in differentiated effector T cells that coordinate ongoing immune responses. Here we demonstrate that human effector CD4 T cells up-regulate the expression of the CD3zeta-related FcRgamma signaling subunit that becomes part of an altered TCR/CD3 signaling complex containing CD3epsilon, but not CD3zeta. The TCR/CD3/FcRgamma complex in effector cells recruits and activates the Syk, but not the ZAP-70, tyrosine kinase. This physiologic switch in TCR signaling occurs exclusively in effector, and not naive or memory T cells, suggesting a potential target for manipulation of effector responses in autoimmune, malignant, and infectious diseases.
Krishnan
Sandeep
S
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Warke
Vishal G
VG
Nambiar
Madhusoodana P
MP
Tsokos
George C
GC
Farber
Donna L
DL
D000328:Adult; D017252:CD3 Complex / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D007399:Interphase / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C115335:CD3E protein, human; D004792:Enzyme Precursors; D018984:Epitopes, T-Lymphocyte; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG; C054979:antigen T cell receptor, zeta chain; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human