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The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the antigen recognition activation motif (ARAM)] that is contained in the TCR zeta and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of several cellular substrates, including the(More)
Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional(More)
The Src-family and Syk/ZAP-70 family of protein tyrosine kinases (PTK) are required for T cell receptor (TCR) functions. We provide evidence that the Src-family PTK Lck is responsible for regulating the constitutive tyrosine phosphorylation of the TCR zeta subunit in murine thymocytes. Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient(More)
A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II-deficient mice were engineered to express Ealpha chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E(More)
The T cell antigen receptor (TCR)-CD3 complex is unique in having ten cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). The physiological importance of this high TCR ITAM number is unclear. Here we generated 25 groups of mice expressing various combinations of wild-type and mutant ITAMs in TCR-CD3 complexes. Mice with fewer than seven(More)
T cells undergo negative selection in the thymus to eliminate potentially autoreactive cells. The signals generated through the alphabeta TCR following receptor interactions with peptide/MHC complexes in the thymus control these selection processes. Following receptor ligation, a fraction of the TCR zeta subunit appears as two distinct(More)
The CD3 epsilon subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 epsilon, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 epsilon to complex a subset of acidic phospholipids,(More)
T cell receptor (TCR) signal transduction is mediated by the immunoreceptor tyrosine-based activation motifs (ITAM). The ten ITAM in the TCR complex are distributed in two distinct signaling modules termed TCR zetazeta and CD3 gammaepsilon/deltaepsilon. To delineate the specific role of the zeta ITAM in T cell development and TCR signal transmission, we(More)
The LspA proteins (LspA1 and LspA2) of Haemophilus ducreyi are necessary for this pathogen to inhibit the phagocytic activity of macrophage cell lines, an event that can be correlated with a reduction in the level of active Src family protein tyrosine kinases (PTKs) in these eukaryotic cells. During studies investigating this inhibitory mechanism, it was(More)