The constitutive tyrosine phosphorylation of CD3zeta results from TCR-MHC interactions that are independent of thymic selection.
The TCR complex, when isolated from thymocytes and peripheral T cells, contains a constitutively tyrosine-phosphorylated CD3zeta molecule termed p21. Previous investigations have shown that the constitutive phosphorylation of CD3zeta results from TCR interactions with MHC molecules occurring in both the thymus and the periphery. To determine what contribution the selection environment had on this constitutive phosphorylation, we analyzed CD3zeta from several distinct class I- and II-restricted TCR-transgenic mice where thymocyte development occurred in either a selecting or a nonselecting MHC environment. Herein, we report that constitutively phosphorylated CD3zeta (p21) was present in thymocytes that developed under nonselecting peptide-MHC conditions. These findings strongly support the model that the TCR has an inherent avidity for MHC molecules before repertoire selection. Biochemical analyses of the TCR complex before and after TCR stimulation suggested that the constitutively phosphorylated CD3zeta subunit did not contribute to de novo TCR signals. These findings may have important implications for T cell functions during self-MHC recognition under normal and autoimmune circumstances.
Becker
Amy M
AM
Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
DeFord-Watts
Laura M
LM
Wuelfing
Christoph
C
van Oers
Nicolai S C
NS
D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine