Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.
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PMID:Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain. 8

The alpha beta T-cell receptor (TCR) recognizes antigenic peptides bound to major histocompatibility complex (MHC) molecules. In contrast to the antibody combining site, for which the antigen contact or complementarity-determining residues (CDRs) have been precisely defined, the location and function of the corresponding CDR regions of the alpha and beta TCR chains are not known. To develop a model system for systematic analysis of the CDRs of the alpha beta TCR, we isolated a panel of murine T-cell clones that recognize a lysozyme peptide containing residues 74-88 bound to either Ab or Abm-12 MHC class II molecules. Although these two MHC molecules differ by only three amino acid residues within the A beta chain, each of the T-cell clones was specific for peptide bound to the self-MHC molecule and did not recognize the same peptide bound to the other MHC molecule. The structural basis for this exquisite ligand specificity of the TCRs was analyzed by isolation and characterization of alpha and beta chain genes from five closely related T-cell clones. Comparison of predicted amino acid sequences mapped the ligand specificity differences to residues present within the alpha chain variable region segment and the alpha and beta chain variable-joining region junction regions. Thus with current models of TCR-ligand interactions, the results suggest that residues 26-30 of the alpha chain variable region may constitute one of the CDR regions of the TCR.
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PMID:Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to Ab or Abm-12 molecules. 131 73

A murine B-cell lymphoma bearing the class II major histocompatibility complex molecule I-Ak was cultured with the protein antigen hen egg white lysozyme (HEL). The I-Ak molecules were purified, and their associated peptides were extracted for characterization. Five HEL peptides were identified. Four contained the 10 amino acid residues HEL 52-61 (DYGILQINSR) but were heterogeneous in length and flanking residues. This core sequence is known to confer a high binding affinity for I-Ak. One additional peptide contained the amino acid residues HEL 48-60. These data demonstrate that the HEL epitope containing residues 52-61 is the most abundant HEL epitope presented on the major histocompatibility complex of the antigen-presenting cells and consequently explains its immunodominance.
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PMID:Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak. 132 33

Diabetes in the non-obese diabetic (NOD) mouse is a multigenic autoimmune disease and is possibly controlled by three recessive loci, including one that is linked to the major histocompatibility complex (MHC). The first external domain of the Class II MHC I-A beta chain in these mice is unique and has been suggested as being responsible for autoimmunity. The I-A alpha chain in these mice is I-A alpha d, and they lack the expression of I-E molecules. We have investigated immune responses to various Ir gene control antigens in NOD mice to determine the influence of the NOD Ia and particularly the I-A beta chain. We find that sheep insulin is highly immunogenic while other insulins are weakly immunogenic in these mice. Hen egg lysozyme, pigeon cytochrome C and the synthetic polypeptide Poly 18, Poly EYK(EYA)5 antigen produce good antibody responses. Apart from H-2d, NOD are the only mice where Poly 18 antigen is immunogenic. In these mice Poly 18 induced good T-cell proliferative response, which was inhibited by anti-Ia antibody, and the mice were able to respond to tyrosine-containing polypeptide Poly EYA but not to the phenylalanine-containing antigen Poly EFA. We also found that synthetic peptide 48-60 of the NOD I-A beta chain is highly immunogenic in syngeneic NOD mice both for T cells and B cells. Using an I-A beta chain-specific monoclonal antibody, we are able to prevent induction of diabetes when the antibody was administrated in prediabetic, young mice. Our results suggest that the immune response to various antigens and autoimmune diabetes in NOD mice is directly influenced by the I-A beta chain.
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PMID:Role of the first external domain of I-A beta chain in immune responses and diabetes in non-obese diabetic (NOD) mice. 170

T lymphocytes recognize discrete regions on an antigen. The specificity of the T cell responses in three mouse strains of differing major histocompatibility complex (MHC) haplotype to a protein antigen, lysozyme, was analyzed using a series of peptides that walk the antigen in single amino acid steps. These peptide series were synthesized using the pin synthesis system, which was modified to allow the peptides to be cleaved from the pins into a physiological buffer free of toxic compounds. This methodology overcomes many of the problems associated with the production of peptides for screening proteins for antigenic determinants. The T cell determinants for the three strains were markedly different. This result points out the limitations of algorithms predicting determinants without reference to the MHC, and the importance of the empirical methodology. This analysis of the T cell response to lysozyme constitutes the most complete study of reactivity to a foreign protein to date and illustrates many important features of antigen recognition by T cells, e.g., presence of major and minor determinant regions. The outer boundaries of each immunogenic region, the determinant envelope, are difficult to define from recently immunized lymph nodes because of the heterogeneity in T cell recognition. However, core sequences common to all the immunogenic peptides in a continuous sequence can be easily defined.
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PMID:T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes. 170 79

We have used the bacterial beta-galactosidase gene (lacZ) as a reporter gene for the rapid measurement of T-cell antigen receptor (TCR)-mediated activation of individual T cells. The reporter construct contained the lacZ gene under the control of the nuclear factor of activated T cells (NF-AT) element of the human interleukin 2 enhancer [Fiering, S., Northrop, J. P., Nolan, G. P., Matilla, P., Crabtree, G. R. & Herzenberg, L. A. (1990) Genes Dev. 4, 1823-1834]. The activity of the intracellular lacZ enzyme was analyzed by flow cytometric measurement of fluorescein accumulation in cells loaded with the fluorogenic beta-galactosidase substrate fluorescein di-beta-D-galactopyranoside. As a model system, the T-cell hybridoma BO4H9.1, which is specific for the lysozyme peptide (amino acids 74-88)/Ab complex, was transfected with the NF-AT-lacZ construct. lacZ activity was induced in 50-100% of the transfectant cells following exposure to pharmacological agents, to the physiological peptide/major histocompatibility complex ligand, or to other TCR-specific stimuli. Interestingly, increasing concentrations of the stimulus increased the fraction of lacZ+ cells, but not the level of lacZ activity per cell. Even under widely varying levels of stimulus, the level of lacZ activity in individual lacZ+ cells remained within a remarkably narrow range. These results demonstrate that TCR-mediated activation can be readily measured in single T cells and strongly suggest that, once committed to activation, the level of NF-AT transcriptional activity in individual T cells is independent of the form or concentration of stimulus. This assay is likely to prove useful for the study of early activation events in individual T cells and of TCR ligands.
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PMID:Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene. 190 76

Antigen-presenting cells (APC) transfected with a construct encoding the hen egg-white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II-restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade.
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PMID:Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells. 191 43

Using a dinitrophenylated and biotinylated peptide antigen, we have developed an affinity chromatography procedure to purify complexes of a given peptide species and a given class II major histocompatibility complex antigen away from class II molecules occupied by other peptides. We show that hen egg lysozyme peptide-I-Ed complexes purified according to this procedure have a greatly enhanced capacity to activate hen egg lysozyme-specific T cells but have lost the capacity to activate three different alloreactive T-cell hybridomas. These data demonstrate that the class II molecule in and of itself is not sufficient to activate alloreactive T cells. Rather, the data suggest that recognition of specific complexes formed between allo-class II and particular autologous peptides may be required. Alternatively, alloreactive T cells may be recognizing "empty" major histocompatibility complex molecules.
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PMID:Self peptide requirement for class II major histocompatibility complex allorecognition. 192 32

The long-standing hypothesis that tolerance to self antigens is mediated by either elimination or functional inactivation (anergy) or self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral lymphoid organs of transgenic mice expressing lysozyme and anti-lysozyme immunoglobulin genes, but are eliminated in similar transgenic mice expressing anti-major histocompatibility complex immunoglobulin genes. By modifying the structure of the lysozyme transgene and the isotype of the anti-lysozyme immunoglobulin genes, we demonstrate here that induction of anergy or deletion is not due to differences in antibody affinity or isotype, but to recognition of monomeric or oligomeric soluble antigen versus highly multivalent membrane-bound antigen. Our findings indicate that the degree of receptor crosslinking can have qualitatively distinct signalling consequences for lymphocyte development.
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PMID:Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. 194 35

A way to study the role of intracellular trafficking of an antigen in its presentation to T cells is to target the antigen to various cell compartments of the antigen-presenting cells (APC) and compare the nature of the complexes associating major histocompatibility complex (MHC) molecules and antigenic peptides, expressed on the cell surface. MHC class I+ and MHC class II+ mouse L fibroblasts secreting hen egg lysozyme (HELs cells) or expressing HEL in their cytosol (HELc cells) were obtained after transfection with HEL cDNA and signal sequence-deleted HEL cDNA, respectively. HEL was evidenced in both HELs- and HELc-transfected cells and the former type of transfectant secreted a large amount of HEL. However, HEL produced in the cytosol exhibited a short half-life of less than 5 min. HEL-derived peptides could not be shown biochemically either in HELc- nor in HELs-transfected cells. We then studied the capacity of these cells to present HEL to HEL-specific class I- and class II-restricted T cells. Both cell types could be recognized by the HEL-specific MHC class I-restricted CTL clones. In contrast, MHC class II-HEL peptide complexes, recognized by HEL-specific helper T cell hybridomas, could be detected on MHC class II+ HELs- but not HELc-transfected cells. In vivo experiments showed, however, that HELc-transfected cells could provide host APC with HELc-derived peptides able to associate with MHC class II molecules. This was inferred from the capacity of MHC class II-HELc-transfected cells, unable by themselves to elicit any anti-HEL antibody response, to prime syngeneic and allogeneic mice against HEL. The priming was revealed by the induction of an antibody response after a boost with an amount of HEL unable itself to elicit an antibody response.
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PMID:Cytosolic targeting of hen egg lysozyme gives rise to a short-lived protein presented by class I but not class II major histocompatibility complex molecules. 200 14


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