Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cell recognition of foreign Ag/MHC class II complexes is sensitive down to approximately 100 complexes per cell or approximately 0.2 complexes/micron2. To better understand the physical basis of the recognition stage of Ag presentation, we examined adhesion of the lysozyme- specific T cell hybridoma, 3A9, to artificial bilayers containing covalent MHC class II/peptide complexes or adhesion molecules. Adhesion of 3A9 cells required a superphysiologic density of the MHC class II/peptide complex and was partly dependent on CD4; cells adhered but did not crawl. No adhesion was observed to bilayers containing MHC class II molecules without the lysozyme peptide. Activated 3A9 cells adhered and crawled on bilayers containing ICAM-1. The physical strength of contacts was tested with fluid shear. 3A9 cells adherent to bilayers containing MHC class II/peptide complexes shed their contact, which remained on the substrate and contained TCR. In contrast, 3A9 cells peeled from the ICAM-1 bilayer, and held firmly on LFA-1 bilayers; in a manner dependent on filamentous actin. When ICAM-1 and the MHC/peptide complexes were combined, the 3A9 cells adhered tightly and spread, but did not crawl, on the bilayers and TCR clustered at the center of the contact area. Physiologically, the TCR is unlikely to directly initiate adhesion. TCR clusters formed with the assistance of adhesion mechanisms may have to be shed to allow de-adhesion, and this may contribute to TCR down-regulation.
...
PMID:TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified MHC class II/peptide complexes and receptor shedding during detachment. 875 22

A high proportion (up to 30%) of major histocompatibility complex (MHC) class II-bound peptides in the mouse and humans contains a proline residue at the N-terminal penultimate position (XP motif). We used a set of ovalbumin (OVA)-specific and hen egg lysozyme (HEL)-specific T cell hybridomas and asked whether the XP motif in MHC class II-associated peptides might influence the stimulation of T cells. We created N-terminally substituted variants of OVA323-339, an H2-Ad restricted OVA epitope and of HEL50-63, a dominant epitope in the context of H2-Ak. Our results show that the N-terminal sequence of MHC class II-bound peptides has a strong impact for the overall stimulation of specific T cells. Proline at the N terminus of antigenic peptides, in contrast to other amino acids, is tolerated or even enhances the recognition of MHC class II-bound peptides significantly.
...
PMID:A biological function for the XP motif within the N terminus of major histocompatibility complex class II-associated peptides. 876 27

T2 cells have a large homozygous deletion in the MHC II region. Transfection of MHC class II genes into T2 cells allows presentation of peptide but not native protein Ags. This defect in protein presentation has been attributed to the lack of HLA-DM, an MHC class II-related protein that facilitates the release of an invariant chain peptide (CLIP) intermediate from nascent MHC class II proteins within the endocytic compartment of APC. Here, we show that Ak molecules within isolated late endosome fractions of T1.Ak (wild-type) vs T2.Ak (HLA-DM-deficient) bind biotin-HEL46-61 at comparable levels, consistent with previous observations that Ak molecules on T2 cells are not predominantly occupied with CLIP. However, Ak molecules in the late endosomes of T2.Ak fail to present peptide to a T hybrid, whereas the late endosomes from T1.Ak have no such defect. Transfection of HLA-DM A and B into T2.Ak partially restores protein Ag presentation by T2.Ak cells. These data suggest that HLA-DM can play a role in Ag presentation in addition to its role in CLIP release. However, even after DM transfection there remains a 10-fold difference in the dose-response curve for hen egg lysozyme presentation by T1.Ak vs T2.Ak/DM cells. In addition, HLA-DM transfection fails to restore presentation by late endosome fractions. The failure to fully restore Ag presentation in T2.Ak cells by DM transfection suggests that another gene product, required for efficient Ag presentation, may be absent from the late endosomes of T2.
...
PMID:Effect of HLA-DM transfection on hen egg lysozyme presentation by T2.Ak cells. 880 21

Self proteins are processed and presented by APCs in the same way as foreign proteins. Presentation of fragments derived from self proteins does not, however, lead to Th cell stimulation because of T cell tolerance. In this study, a novel approach was used to investigate whether B cell tolerance toward a self Ag could be due to the absence of this Th cell recognition. The highly conserved nonimmunogenic protein ubiquitin was used as a model protein. Two modified ubiquitin molecules were constructed with ubiquitin segments exchanged either with the T cell epitope, OVA(325-336), which binds to the mouse A(d) MHC class II molecule, or with the T cell epitope, hen egg lysozyme(50-61), which binds to the A(k) molecule. Mice were immunized with the resulting proteins. Both modified proteins elicited strong autoantibody responses toward soluble native ubiquitin, demonstrating that insertion of a single foreign T cell epitope can overcome the B cell nonresponsiveness. The T cell regulatory role of one of the inserted foreign T cell epitopes in ubiquitin was studied, and at least two different Th cell specificities were found to operate in the response. The T cells were directed against: 1) the inserted epitope, and 2) a combination of the inserted epitope and parts of the neighboring ubiquitin regions. Therefore, the absence of T cell help seems to be an important reason for B cell tolerance toward self proteins.
...
PMID:Breaking of B cell tolerance toward a highly conserved self protein. 894 81

The possibility of inducing antigen-presenting capacity in cells normally lacking such capacity, currently represents a major goal in vaccine research. To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule. To minimize the cytopathic effect and to improve safety, in view of possible in vivo applications, we made this rVV replication incompetent by Psoralen and long wave UV treatment. Tumor cells infected with rVV encoding I-Ak alone, pulsed with hen egg white lysozyme peptide (HEL46-61), induced IL-2 secretion by an antigen-specific T hybridoma. Tumor cells infected with the rVV encoding mB7-1 provided costimulation for activating resting CD4+ T cells in the presence of ConA. Tumor cells infected with the rVV encoding I-Ak and mB7-1, and pulsed with chicken ovotransferrin peptide (conalbumin133-145), induced a significantly higher response in a specific Th2 cell clone (D10.G4.1) as compared to cells infected with rVV encoding I-Ak molecules only. Thus, this replication incompetent rVV represents a safe, multiple gene, vector system able to confer in one single infection step effective APC capacity to non-professional APCs.
...
PMID:Induction of antigen-presenting capacity in tumor cells upon infection with non-replicating recombinant vaccinia virus encoding murine MHC class II and costimulatory molecules. 900 58

Major histocompatibility complex (MHC) class II molecules bind antigenic peptides for display to T lymphocytes. Although the enzymes involved remain to be identified, it is commonly believed that class II associated peptides are released from intact antigens through a series of proteolytic steps carried out inside antigen presenting cells. We have examined the effect of amino acid substitutions on proteolytic processing of the model antigen hen-egg lysozyme (HEL). Altered HEL molecules, engineered by site-directed mutagenesis of a HEL cDNA, were expressed as separate stable transfectants in a B cell lymphoma line. Each transfectant processed a different mutant HEL protein for presentation on MHC class II. We purified the resulting class II-associated peptides and analyzed them by mass spectrometry. Our results strongly support the hypothesis that antigen processing continues after peptide binding to the MHC class II molecule and are most consistent with a scenario in which long peptides first bind to MHC class II and are then trimmed by exopeptidase.
...
PMID:Amino-terminal trimming of peptides for presentation on major histocompatibility complex class II molecules. 901 35

Covalent conjugates of hen egg lysozyme (HEL) and anti-major histocompatibility complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice intranasally. Three weeks after intranasal (IN) priming, mice responded rapidly to IN challenge with a mixture of HEL and cholera toxin (CT), by producing large titres of anti-HEL IgA and IgG1 antibody in serum, and IgA antibody in nasal secretions. No secondary response to HEL plus CT occurred in mice that received no priming or mice primed with HEL alone. The secondary serum IgG antibody response was dominated by the IgG1 subclass. HEL combined with CT adjuvant worked much better than HEL alone in producing the secondary response. Control conjugates, containing an IgG isotype-matched mAb without specificity for mouse tissues, provided poor priming. Mice expressing MHC class II molecules, to which the anti-MHC II mAb could not bind, produced a weak antibody response compared with those that expressed the appropriate. MHC class II molecule. Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract.
...
PMID:Intranasal antigen targeting to MHC class II molecules primes local IgA and serum IgG antibody responses in mice. 915 36

Here we describe generation of Aw3.18, a monoclonal antibody that recognizes peptide residues 48-62 of hen egg lysozyme (HEL) bound to the MHC class II molecule I-Ak. Epitope mapping revealed that Aw3.18 detects a change in the solvent-exposed surface of this peptide-MHC complex upon substitution of the peptide side chain at position P1. Furthermore, Aw3.18 blocked recognition by some, but not all, of the HEL 48-62-reactive T cell hybridomas tested, suggesting a heterogeneity in the T cell response toward this complex. Finally, using Aw3.18, it was possible to determine the fraction of I-Ak molecules loaded with 48-62 peptide after culture of an antigen-presenting cell in medium containing HEL.
...
PMID:Characterization and quantitation of peptide-MHC complexes produced from hen egg lysozyme using a monoclonal antibody. 920 45

Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12-deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide-major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61-Ak complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II-associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand-bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation.
...
PMID:Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro. 927 83

We investigated in H-2k mice bearing a genetically disrupted invariant chain (Ii) gene, the MHC class II expression and antigen presentation ability of dendritic cells (DC) freshly purified from the spleen (SpDC) or derived from bone marrow precursors (BMDC) upon treatment with GM-CSF. In the absence of Ii, class II alpha/beta heterodimers are expressed on the DC membranes to a similar extent than in control mice, in contrast to splenic B cells. Class II molecules immunoprecipitated from the plasma membrane of Ii deficient DC are compact indicating that the dimers are stabilized by antigenic peptides. Furthermore DC from Ii mutant mice are able to present to CD4+ T lymphocytes, epitopes derived from the processing of the hen egg lysozyme (HEL) that normally require expression of the Ii molecule for presentation by B cells. All together, our results show that the antigen processing machinary of DC provides peptides that can reach class II molecules and stabilize their conformation in the absence of Ii mediated targeting of class II complexes.
...
PMID:Dendritic cells from mice lacking the invariant chain express high levels of membrane MHC class II molecules in vivo. 928 61


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

---