T cell receptors stimulation

Yamamoto, T., Hattori, M., and Yoshida, T. 2007. Induction of T-cell activation or anergy determined by combination of intensity and duration of T-cell receptor stimulation, and sequential induction in an individual cell. Immunology 121 383-391. 

Jenne, D. E, and Tschopp, J. (1988). Granzymes, a family of serine proteases released from granules of cytolytic T lymphocytes upon T cell receptor stimulation, Immunol. Rev. 103, 53-71. 

Intratracheal instillation of sihca (20 mg in 50 (ji sterile saline) into BALB/c mice reduced mitogenic responses to T cell receptor stimulation, and markedly increased activation-induced cell death, compared with control lymphocytes from sahne-instilled mice (Borges et al. 2002). CD4 T cell death was mediated by Fas ligand, because CD4 T cells from Fas ligand-deficient gld mice did not suffer activation-induced apoptosis. 

Devadas, S., Zaritskaya, L., Rhee, S.G., Oberley, L. WiUiams, M.S. (2002). Discrete generation of supetoxide and hydrogen peroxide by T cell receptor stimulation selective regulation of mitogen-activated protein kinase activation and fas ligand expression. The Journal of Experimental Medicine, 195, 59-70. 

SHIPl (hereafter SHIP) was identified in the early 1990s as a 145 kDa intracellular protein that is tyrosine phosphorylated upon the stimulation of hemeatopoietic cells via B and T-cell receptor, and by multiple cytokines (Damen et al, 1996, Lioubin et al. 1996). Molecular cloning of cDNA for SHP revealed that the molecule consists of an N terminal SH2 domain, a highly conserved, centrally located motif having Ptdins 5-phosphatase activity, two NPXY sequmces, which are phosphorylated on Tyr upon various stimuli and a proline-rich C terminus (Figure 2). SHIP hydrolyses PtdIns(3,4,5)/ 3, and inositol 1,3,4,5-tetrakisphosphate both in vitro and in vivo, thus belongs to the type n 5-phosphatases, charactaized also by their... 

In the case of TSST-1, T-cell activation may be influenced by peptide in the antigen-binding groove of HLA-DR as per contact with the C-terminus ofTSST-1. Specifically, histidines 132, 135, and 140 ofTSST-1 are important for T-cell receptor interactions plus stimulation of proinflammatory cytokine production. This is readily demonstrated by in vitro and in vivo studies with these toxin mutants, which also represent promising... 

Ironically, SE or TSST-1 concentrations that cause T-cell proliferation do not always correlate with receptor affinity. For instance, SEE binds HLA-DR with 100-fold lower affinity relative to the very similarly structured SEA however, SEE stimulates T-cell proliferation to equivalent levels as SEA. The dose-response curves for cytokine and chemokine production in vitro by staphylococcal superantigen-stimulated cells are also very similar despite differences in affmity/specificity for major histocompatibility complex class II and T-cell receptor V/3 molecules. Overall, these observations suggest that the biological effects of staphylococcal superantigens are induced at rather low, nonsaturating occupancy rates not readily classified by typical biokinetics. 

B lymphocytes, which as APCs present viral fragments on their surfaces, are recognized by helper T cells (blue) or their T cell receptors (9). Stimulated by interleukins, selective clonal replication then takes place of B cells that carry antigen receptors matching those of the pathogen (10). These mature into plasma cells (11) and finally secrete large amounts of soluble antibodies (12). 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

The further com e of signal transduction is variable. The following signaling pathways are activated following stimulation of T cell receptors ... 

It is now possible to identify T-cell epitopes, which are recognized by receptor complexes on the T-lymphocyte surface, in addition to the B-cell epitopes recognized by antibodies (which are also the B-lymphocyte receptors). T-cells are stimulated by small peptide fragments of antigens produced by intracellular proteolytic processing, so problems of conformation do not arise, and syn-... 

A variation of the pharmacophore library was seen in an approach used to determine CD4+ T cell epitopes.31 In a 14-mer peptide, the researchers keep residues in positions 1, 4, and 6 constant since they functioned as anchor positions for binding receptor, and proceeded to vary the other residues in the peptide. This allowed the use of a shorter synthetic route compared to one that would be needed if all positions were to be varied. Limiting the size of the library allowed the authors to obtain better assays. By doing a partial release of the peptides, the authors were able to find the final peptide that represented the epitope of the T cell receptor. In another example, the epitope to inhibit stimulation of the thyrotropin receptor also was found via combinatorial libraries.32 Since the synthesis of a totally random hexapeptide library was deemed impractical, the authors opted to hold one position constant while the other five residues were randomized. This method was repeated for each residue in the peptide. The residues that were determined to be the most active were used as a basis for a second-generation library. The only limitation of the library was not the quantity of product synthesized, but to properly pinpoint the peptides in an assay. 

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