title: T cell antagonism is functionally uncoupled from the 21- and 23-kDa tyrosine-phosphorylated TCR zeta subunits.
abstract: The functional effects of altered peptide ligands on T cells is proposed to involve differential intracellular signaling mediated by the 21- and 23-kDa tyrosine-phosphorylated derivatives of the TCR zeta subunit (p21 and p23). To understand the functional contribution of p21 and p23 to T cell development and T cell antagonism, we generated selected TCR zeta transgenic mice maintained on the P14 alphabeta TCR transgenic line such that p23 or both p21 and p23 were selectively eliminated. Importantly, one line (YF1,2) retains the constitutively tyrosine-phosphorylated p21 in the complete absence of inducible p23. We determined that T cell development was uncoupled from p21 and/or p23. Using a series of agonist, weak agonist, and antagonist peptides, we analyzed the role of each of the phosphorylated forms of TCR zeta on T cell activation and antagonism. In this study, we report that the proliferative responses of alphabeta P14 T cells to agonist peptides and the inhibition of proliferation resulting from antagonist peptide treatments was functionally uncoupled from p21 and/or p23. These results suggest that the mechanism of T cell antagonism is independent of the two phosphorylated TCR zeta derivatives.
authors.affiliation: Center for Immunology and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Pitcher
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
authors.forename: Nicolai S C
authors.initials: NS
authors.lastname: van Oers
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D010446:Peptide Fragments; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine; D010649:Phenylalanine