Expression and tyrosine phosphorylation of the T cell receptor zeta-subunit in human thymocytes.
Recent evidence suggests that the zeta-subunit of the TCR complex plays a critical role in transducing signals initiated by the Ag receptor heterodimer. Because thymic maturation involves specific interactions between the TCR complex and thymic stromal cells, the zeta-subunit has been postulated to also play a role in this process. To assess the potential for zeta to contribute to thymocyte maturation, we have used an anti-zeta mAb (TIA-2) to quantitate its expression in mature (CD3bright) and immature (CD3dim and CD3-) populations of human thymocytes. Using both flow cytometric and immunoblotting analysis, we found that the relative expression of TCR-zeta varied directly with the surface expression of CD3. Importantly, TCR-zeta was detected in the majority of CD3- thymocytes, indicating that its expression precedes the surface appearance of CD3:TCR. In thymocytes, TCR-zeta was found to be constitutively phosphorylated on tyrosine residues. The relative expression of phospho-zeta varied directly with the maturational stage of the thymocyte, with the mature (CD3bright), single positive cells accounting for most of the phospho-zeta found in the human thymus. The expression of phospho-zeta could be significantly increased by activating thymocytes with mAb reactive with either CD3 or CD2. These results suggest that TCR-zeta is functionally linked to the major thymocyte activation receptors.
Vivier
E
E
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Morin
P
P
Tian
Q S
QS
Daley
J
J
Blue
M L
ML
Schlossman
S F
SF
Anderson
P
P
D002454:Cell Differentiation / Q000276:immunology; D002675:Child, Preschool; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins; D010766:Phosphorylation; D019000:Phosphotyrosine; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine; D014443:Tyrosine