Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of 25 mRNAs in a single human lymphocyte was investigated using the reverse transcription nested polymerase chain reaction (RT nested PCR) method. Proteins corresponding to the mRNA investigated were mucin antigen, melanoma antigen, pregnancy-specific beta-1 glycoprotein 4, phenylethanolamine-N-methyl-transferase, beta B3-crystallin, homeobox 4A, interleukin 2, cluster of differentiation 8, progesterone receptor, parathyroid hormone, gastrin, cholecystokinin/pancreozymin, glucagon, insulin, enkephalin, thyroid stimulating hormone, adrenocorticotropic hormone, synapsin I, immunoglobulin (Ig)M, IgD, IgG1, IgG3, IgE, IgA, and T cell receptor alpha. All mRNAs were detected in single lymphocytes of two individuals, without exception. In addition, transcripts of IgM, IgD, IgG1, IgG3, IgE, IgA, and the T cell receptor a gene were detected in single sperms. The results strongly suggest the possibility that all mRNAs may be expressed in a single human cell, of both somatic and germ lineage. Thus, cells can consume energy in vain to produce functionally meaningless gene transcripts. However, this basal or illegitimate transcription may be essential for the birth of living matter: the arrow of time in a cell. Moreover, the phenomenon implies the potential of using lymphocytes in place of inaccessible tissue for the diagnosis of genetic diseases.
Mol Gen Genet 1998 May
PMID:A single human cell expresses all messenger ribonucleic acids: the arrow of time in a cell. 964 29

The negative regulation of antigen receptor signal transduction is essential for the maintenance of thresholds for activation in lymphocytes. CD45 and SHP-1 are tyrosine phosphatases that are important in maintaining the proper level of tyrosine phosphorylation. Regulation of the src family of tyrosine kinases is mediated by the coordinated action of the tyrosine kinase Csk and the tyrosine phosphatase CD45. B cell receptor signaling is negatively regulated by the recruitment of SHP-1 to bind the B cell transmembrane proteins CD22 and FcgammaRIIb1. SHP-1 also functions to negatively regulate T cell receptor signaling by dephosphorylating and inactivating tyrosine kinases.
J Mol Med (Berl) 1998 Jul
PMID:Negative regulation of antigen receptor signaling in lymphocytes. 969 36

T cell responses are highly specific and T cell receptors (TCRs) can recognise subtle differences in major histocompatibility complex (MHC)-peptide complexes. While nominal peptide antigens usually act as full agonists that trigger the whole spectrum of T cell responses, some peptides exhibiting mutations at the TCR-MHC/peptide contact site stimulate only a fraction of T cell responses (partial agonists) or may even inhibit T cell activation by full agonists (antagonist). The present study analyses mathematically the role of TCR-dimerization for T cell antagonism and T cell specificity in general. It demonstrates that T cell antagonists can effectively inhibit TCR-dimerization and that this mechanism can sufficiently explain all aspects of T cell antagonism. The kinetic model of T cell activation proposes that increasing the time required for effective TCR-signaling is the most effective mechanism to increase the discriminatory capacity of TCRs. Our results indicate that TCR-oligomerization is an alternative and efficient mechanism to ensure T cell specificity.
Mol Immunol 1998 Apr
PMID:The role of T cell receptor dimerization for T cell antagonism and T cell specificity. 974 87

T cell activation rapidly and transiently regulates the functional activity of integrin receptors. Stimulation of CD3/T cell receptor, CD2 or CD28, as well as activation with phorbol esters, can induce within minutes an increase in beta1 integrin-mediated adhesion of T cells to fibronectin. In this study, we have produced and utilized a mutant of the Jurkat T cell line, designated A1, that lacks protein and mRNA expression of the beta1 integrin subunit but retains normal levels of CD2, CD3, and CD28 on the cell surface. Activation-dependent adhesion of A1 cells to fibronectin could be restored upon transfection of a wild-type human beta1 integrin cDNA. Adhesion induced by phorbol 12-myristate 13-acetate-, CD3-, CD2-, and CD28 stimulation did not occur if the carboxy-terminal five amino acids of the beta1 tail were truncated or if either of two well-conserved NPXY motifs were deleted. Scanning alanine substitutions of the carboxy-terminal five amino acids demonstrated a critical role for the tyrosine residue at position 795. The carboxy-terminal truncation and the NPXY deletions also reduced adhesion induced by direct stimulation of the beta1 integrin with the activating beta1 integrin-specific mAb TS2/16, although the effects were not as dramatic as observed with the other integrin-activating signals. These results demonstrate a vital role for the amino-terminal NPXY motif and the carboxy-terminal end of the beta1 integrin cytoplasmic domain in activation-dependent regulation of integrin-mediated adhesion in T cells. Furthermore, the A1 cell line represents a valuable new cellular reagent for the analysis of beta1 integrin structure and function in human T cells.
Mol Biol Cell 1998 Oct
PMID:Use of a beta1 integrin-deficient human T cell to identify beta1 integrin cytoplasmic domain sequences critical for integrin function. 976 39

To study how the T cell receptor interacts with its cognate ligand, the MHC/peptide complex, we used site directed mutagenesis to generate single point mutants that alter amino acids in the CDR3beta loop of a H-2Kb restricted TCR (N30.7) specific for an immunodominant peptide N52-N59 (VSV8) derived from the vesicular stomatitis virus nucleocapsid. The effect of each mutation on antigen recognition was analyzed using wild type H-2Kb and VSV8 peptide, as well as H-2Kb and VSV8 variants carrying single replacements at residues known to be exposed to the TCR. These analyses revealed that point mutations at some positions in the CDR3beta loop abrogated recognition entirely, while mutations at other CDR3beta positions caused an altered pattern of antigen recognition over a broad area on the MHC/peptide surface. This area included the N-terminus of the peptide, as well as residues of the MHC alpha1 and alpha2 helices flanking this region. Assuming that the N30 TCR docks on the MHC/peptide with an orientation similar to that recently observed in two different TCR-MHC/peptide crystal structures, our findings would suggest that single amino acid alterations within CDR3beta can affect the interaction of the TCR with an MHC surface region distal from the predicted CDR3beta-Kb/VSV8 interface. Such unique recognition capabilities are generated with minimal alterations in the CDR3 loops of the TCR. These observations suggest the hypothesis that extensive changes in the recognition pattern due to small perturbations in the CDR3 structure appears to be a structural strategy for generating a highly diversified TCR repertoire with specificity for a wide variety of antigens.
Mol Immunol 1998 Jul
PMID:Point mutations in the beta chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I/peptide complex over a broad interface area. 982 58

We recently described the generation and expression of a chimeric T cell receptor with specificity for the tumor antigen TAG72 consisting of the single chain antibody (scFv) B72.3-scFv and the gamma chain of the FcepsilonRI receptor. The corresponding chimeric receptor containing the zeta chain of the TCR as signalling unit is not functionally expressed reflecting that the requirements for functional expression of chimeric receptors containing the gamma signalling chain are apparently different compared to those containing the CD3zeta signalling chain of the TCR. We describe a novel set of chimeric anti-TAG72 receptors including in their extracellular moiety the constant immunoglobulin CH2/3 domains that allow stable expression of chimeric gamma as well as zeta receptors. We designed anti-TAG72 receptors that consist of a scFv fragment derived from an anti-TAG72 second generation antibody (CC49) and of the CH2/3 domains of the human IgG and intracellularily either of the zeta or gamma signalling chain. The recombinant CC49-CH2/3-zeta and CC49-CH2/3-gamma DNA, respectively, was transfected into MD45 T cells and expressed under control of the RSV LTR. Both receptors were found on the cell membrane of transfected cells as demonstrated by flow cytometry analysis using an anti-human IgG Fc antibody directed to the CH2/3 immunoglobulin domains of the chimeric receptor. Specific cross-linking of the chimeric zeta as well as the gamma receptor by antigen or anti-human Ig antibodies resulted in specific activation of transfected cells. Our results demonstrate that both the gamma chain and the zeta chain++ containing receptor are stably expressed and convert T cells to specificity for the TAG72 antigen. This receptor design will facilitate efficient generation of genetically modified peripheral T cells and may provide valuable tools for the cellular immunotherapy of TAG72+ tumors.
Int J Mol Med 1998 Jul
PMID:Chimeric anti-TAG72 receptors with immunoglobulin constant Fc domains and gamma or zeta signalling chains. 985 51

B and T cell receptor gene assembly by V(D)J recombination is tightly regulated during lymphoid development. The mechanisms involved in this regulation are poorly understood. Here we show that nucleosomal DNA is refractory to V(D)J cleavage. However, the presence of HMG1, a chromatin-associated nonhistone DNA-binding protein, stimulates V(D)J cleavage of nucleosomal templates. This HMG1 stimulation is differentially affected by the rotational or translational positioning of the recombination signal sequence on the histone octamer, with cleavage of the 12 bp spacer RSS showing sensitivity to rotational position and the 23 bp spacer RSS affected by its displacement from the dyad. These results suggest that V(D)J recombination can be modulated by controlling substrate accessibility and cleavage at the level of an individual nucleosome.
Mol Cell 1998 Dec
PMID:Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1. 988 70

Signaling through A2A adenosine receptors (A2AR) regulates T lymphocyte expansion and modulates T cell receptor (TCR)-mediated effector functions in vitro. To understand the role of A2ARs in the regulation of immune response, we investigated the expression levels of this receptor in different functional lymphocyte subsets. Monoclonal anti-A2AR antibody was used to develop a flow cytometric assay to quantify the expression A2ARs on lymphocytes. We report that detectable levels of expression of A2ARs are much higher among T cells than B cells. More CD4(+) than CD8(+) T cells express A2ARs, but activation of T cells increases A2AR expression, predominantly in CD8(+) T cells. No significant differences were found in the proportion of A2AR+ cells between CD8(low) and CD8(high) T cells or between TCR/CD3(low) and TCR/CD3(high) T cells. Studies of T helper cell subsets (TH1 and TH2) reveal that lymphokine-producing cells are much more likely to express A2ARs than are cells that do not produce lymphokines. These results suggest that A2ARs are variably expressed on T cell subsets and may regulate cytokine production in activated T lymphocytes.
Mol Pharmacol 1999 Mar
PMID:Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies. 1005 47

V(D)J recombination, normally an intramolecular process, assembles immunoglobulin and T cell receptor genes from V, D, and J coding segments. Oncogenic chromosome translocations can result from aberrant rearrangements, such as occur in intermolecular V(D)J recombination. How this is normally prevented remains unclear; DNA cleavage, joining, or both could be impaired when the recombination signal sequences (RSS) are located in trans, on separate DNA molecules. Here, we show that both trans cleavage and joining of signal ends occur efficiently in vivo. Unexpectedly, trans joining of coding ends is severely impaired (100-to 1000-fold), indicating that protection against intermolecular V(D)J recombination is established at the joining step. These findings suggest a novel surveillance mechanism for eliminating cells containing aberrant V(D)J rearrangements.
Mol Cell 1999 Mar
PMID:Intermolecular V(D)J recombination is prohibited specifically at the joining step. 1019 35

We describe here the structure of a murine T cell receptor (TCR) Valpha2.6Jalpha38 (TCRAV2S6J38) domain, derived from a T cell hybridoma with specificity for the H-2Ddmajor histocompatibility complex class I molecule bound to a decamer peptide, P18-I10, from the HIV envelope glycoprotein gp120, determined by X-ray crystallography at 2.5 A resolution. Unlike other TCR Valpha domains that have been studied in isolation, this one does not dimerize in solution at concentrations below 1 mM, and the crystal fails to show dimer contacts that are likely to be physiological. In comparison to other Valpha domains, this Valpha2.6 shows great similarity in the packing of its core residues, and exhibits the same immunoglobulin-like fold characteristic of other TCR Valpha domains. There is good electron density in all three complementarity-determining regions (CDRs), where the differences between this Valpha domain and others are most pronounced, in particular in CDR3. Examination of crystal contacts reveals an association of Valpha domains distinct from those previously seen. Comparison with other Valpha domain structures reveals variability in all loop regions, as well as in the first beta strand where placement and configuration of a proline residue at position 6, 7, 8, or 9 affects the backbone structure. The great variation in CDR3 conformations among TCR structures is consistent with an evolving view that CDR3 of TCR plays a plastic role in the interaction of the TCR with the MHC/peptide complex as well as with CDR3 of the paired TCR chain.
J Mol Biol 1999 Jun 25
PMID:The X-ray crystal structure of a Valpha2.6Jalpha38 mouse T cell receptor domain at 2.5 A resolution: alternate modes of dimerization and crystal packing. 1037 58


<< Previous 1 2 3 4 5 6 7 8 9 10