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

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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)

Genes outside of the mouse major histocompatibility complex (H-2) were found to be capable of specifically reversing the previously described nonresponsiveness to hen egg-white lysozyme (HEL) owing to H-2b immune response (Ir) genes. C3H.SW, BALB.B, and C57L, all of the H-2b haplotype, showed responsiveness to HEL, but not to human lysozyme (HUL). Mapping of the reversing gene(s) was attempted by testing H-2b recombinant inbred (RI) strains of mice carrying C3H, BALB, and C57L non-H-2 genes. Analysis of the strain distribution pattern of responsiveness with both CXB and BXH RI strains was consistent with the location of the responsible site within the H-3 region on chromosome 2. The anti-HEL proliferative responsiveness in two H-3 congenic strains of mice, B10.C(28NX)SN and B10.C-H-3cH-3a, that have BALB/c genes within the H-3 region confirmed the mapping, as well as localized the reversing gene(s) near the Ir-2 gene. The data are discussed with regard to the site of expression of the reversing gene(s) and its mechanism of action.
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PMID:Selective reversal of H-2 linked genetic unresponsiveness to lysozymes. I. Non-H-2 gene(s) closely linked to the Ir-2 locus on chromosome 2 permit(s) an antilysozyme response in H-2b mice. 643 75

The plaque-forming cell (PFC) response to human lysozyme (HUL) is regulated by an Ir gene(s) located within the major histocompatibility complex of the mouse. Mice of H-2a, H-2k, H-2v and H-2r haplotypes respond to HUL, whereas mice with H-2b, H-2d, H-2q, H-2s and H-2u haplotypes fail to generate substantial anti-HUL PFC responses. In contrast, only mice carrying the H-2b and H-2s haplotypes are non-responders to the distantly related hen eggwhite lysozyme (HEL). The major genetic control of the anti-HUL PFC response maps to the I-A subregion of the H-2 complex with perhaps a minor influence by a gene mapping to the right of the I-B subregion. HUL and HEL induce a cross-reactive suppressor cell, directed against a particular determinant found on both lysozymes. Once generated, these antigen-specific suppressor cells can affect the in vitro primary response to either lysozyme conjugated to sheep red blood cells. Despite this overlap, the strain distribution pattern of responsiveness is different for the two lysozymes. In the discussion, this was attributed to the MHC-related failure to process and/or present HEL to the HEL/HUL cross-reactive suppressor T cell in H-2q, d and u strains.
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PMID:Partial overlap of Ir gene-controlled responses to two proteins of limited relatedness: hen egg-white lysozyme and human lysozyme. 644 69

Mice carrying the H-2b and H-2s haplotypes are genetically nonresponsive to hen egg-white lysozyme (HEL). Analysis of the anti-HEL response patterns of F1, F2 and backcross progeny showed that responsiveness was dominant and H-2 linked. From plaque-forming cell and serum assays in intra-H-2 recombinant mice, it was established that two I loci were implicated, the possession of either leading to responsiveness to HEL. One of the I genes maps in I-A, and the second in I-C, S or G. While the nonresponse phenotype was determined by the H-2 haplotype, there were codominant non-H-2 genes which contributed to a severe reduction in the level of antibody produced in responder strains. A model is presented attributing the outcome of an encounter with HEL to the regulatory balance of helper and suppressor T cells, which have been activated by different subregions of the major histocompatibility complex.
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PMID:Multiple H-2 and non-H-2 genes controlling the antilysozyme response: alternative gene constellations can lead to responsiveness. 677 80

Two distinct modes of unresponsiveness to hen egg-white lysozyme (HEL) have been demonstrated in the "nonresponder" C57BL/10 Sn (B 10) mouse strain at the level of T cell proliferation. The first is an apparent inability to respond to a peptide of HEL comprising 70% of the molecule, LII (amino acids 13--105, when HEL is used as immunogen. On its own, LII is capable of eliciting a strong response from B 10 draining lymph node cells, but this capacity is concealed when the whole molecule is used for immunization (by suppressor cell activity raised against another part of HEL, as described by Adorini et al., J.Exp. Med. 1979. 150: 293). In the B 10.A mouse, LII and HEL are equally immunogenic. The second is an actual failure, presumably unrelated to suppression, to contrive a response to particular determinants on HEL, demonstrated for certain epitopes on LII and LIII (amino acids 106--129). Such a failure to respond was maintained despite an increase in the immunizing dose of peptide to a molarity at which HEL itself could overcome Ir gene control. B 10 cells responding to a high dose of HEL, or to the immunogenic lysozyme from ring-neck pheasant, were also unable to respond to these epitopes. These deficits in responsiveness appear to be characteristic manifestations of the relevant haplotype of the major histocompatibility complex. They may not only reflect the balance between competing T cell subpopulations, but also the constraints of associative recognition that may underlie the presentation of particular antigenic specificities.
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PMID:Ir-gene control of T cell proliferative responses: two distinct expressions of the genetically nonresponsive state. 677 81

Antigen-pulsed neutrophils from mouse peritoneal cavities displayed a remarkable level of lymphocyte proliferative activities to antigen-primed T lymphocytes. Genetic mapping studies demonstrated that compatibility at the I-A, as well as I-E/C, subregions of the major histocompatibility complex (MHC) was essential for effective presentation of the lysozyme antigen. These antigen-presenting activities were remarkably inhibited by anti-Ia sera. Inhibition tests revealed that neutrophil immune-associated (Ia) antigens seem to be essential for antigen presentation during the initial 8 hr. Elimination studies of antigen-pulsed neutrophils with alloantisera plus complement revealed these antigen-presenting neutrophils bearing both I-A and I-E/C gene products on the same cells. These results suggest that Ia-positive neutrophils might play a role in the immune response through antigen presentation.
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PMID:Antigen-pulsed neutrophils bearing Ia antigens can induce T lymphocyte proliferative response to the syngeneic or semisyngeneic antigen-primed T lymphocytes. 696 41

Chloroquine treatment of antigen-presenting cells (APC) was explored as a tool to investigate the processing pathway for major histocompatibility complex (MHC) class II-restricted presentation of the endogenous secreted hen egg lysozyme (HEL) and transmembrane measles virus haemagglutinin (HA). A 72-hr pretreatment of the APC with 25 microM chloroquine blocked the presentation of the HEL(52-61) T-cell epitope generated from endogenous HEL to the I-Ak-restricted 3A9 T-cell hybridoma by MHC class II-transfected L cells expressing the invariant chain (Ii). The presentation of exogenously added HEL peptides was not affected. Under the same conditions, no inhibition of the presentation of HEL(106-116) to the I-Ed-restricted G28 high-avidity T-cell hybridoma, nor of HA when synthesized by L cells, was observed. When B-lymphoid APC were used, inhibition was observed in every case with a low number of B APC pretreated for 48 hr with chloroquine prior to the T-cell stimulation test. Moreover, addition of chloroquine to untreated B APC during the T-cell stimulation assay was sufficient to inhibit completely the presentation of HEL(106-116) to the B10.D24.42 low avidity T-cell hybridoma. Altogether these studies suggest that an apparent resistance of endogenous Ag presentation to chloroquine inhibition may not necessarily indicate the existence of a non-endosomal pathway but may be due to the nature of the T-cell epitope, to the use of 'non-professional' APC such as L cells, to the use of T cells of high avidity, and to high amounts of pre-existing MHC class II-peptide complexes expressed by the APC. We demonstrate here that, at least in conventional APC such as B cells, class II-restricted presentation of both endogenous secreted HEL and transmembrane HA involves an endosomal pathway.
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PMID:Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell. 750 20

Hen egg lysozyme 52-61-specific CD4+ T cells responded by interleukin 2 (IL-2) secretion to any peptide containing this epitope regardless of length of NH2- and COOH-terminal composition. However, CD4- variants could only respond to peptides containing the two COOH-terminal tryptophans at positions 62 and 63. Substitutions at these positions defined patterns of reactivity that were specific for individual T cells inferring a T cell receptor (TCR)-based phenomenon. Thus, the fine specificity of major histocompatibility complex (MHC)-peptide recognition by the TCR was dramatically affected by CD4 and the COOH-terminal peptide composition. Peptides that failed to induce IL-2 secretion in the CD4- variants nevertheless induced strong tyrosine phosphorylation of CD3 zeta. Thus, whereas the TCR still recognized and bound to the MHC class II-peptide complex resulting in protein phosphorylation, this interaction failed to induce effective signal transduction manifested by IL-2 secretion. This provides a clear example of differential signaling mediated by peptides known to be naturally processed. In addition, the external domains of CD4, rather than its cytoplasmic tail, were critical in aiding TCR recognition of all peptides derived from a single epitope. These data suggest that the nested flanking residues, which are present on MHC class II but not class I bound peptides, are functionally relevant.
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PMID:Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor. 751 3

The immune system has evolved the potential to respond to a wide variety of antigens, yet unresponsiveness to many foreign determinants is encountered frequently. Here, we report a lack of response to a particular determinant, hen egg lysozyme (HEL)-(46-61)-peptide (p46-61), in C57BL/6 (H-2b) mice, whereas a strong T-cell response to this determinant is obtained in major histocompatibility complex (MHC)-identical C3H.SW mice. However, (C3H.SW x C57BL/6)F1 mice respond well to p46-61, suggesting the absence of a p46-61-specific "hole" in the T-cell repertoire in C57BL/6 mice. We further show that p46-61 cannot bind the I-Ab class II MHC molecule, whereas p46-60 lacking Arg61 exhibits good binding and is immunogenic in both strains. Thus, the presence of the hindering residue, Arg61, renders p46-61, a dominant determinant in C3H.SW, into a silent, cryptic determinant in C57BL/6 mice. Upon i.p. immunization with HEL, no T-cell responses to either HEL or p46-61 could be demonstrated in spleens of HEL-primed C57BL/6 mice, whereas a predominant response to p46-61 and HEL was demonstrated in C3H.SW mice. Evidently, C57BL/6 mice differ from C3H.SW in their ability to process p46-61 into an actual I-Ab binding determinant, indicating a putative enzymatic defect in the C57BL/6 strain. Furthermore, our results suggest that the inability of C57BL/6 mice to respond in the spleen to HEL is based upon its failure to generate a dominant immunogenic determinant from HEL, coupled with its pattern of susceptibility to regulatory effects.
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PMID:Hindrance of binding to class II major histocompatibility complex molecules by a single amino acid residue contiguous to a determinant leads to crypticity of the determinant as well as lack of response to the protein antigen. 753 99

The recessive mouse mutations lpr and gld create deficiencies in an interacting pair of cell surface molecules, CD95 (Fas/APO-1) and Fas-ligand (FasL), respectively, resulting in autoantibody production resembling human systemic lupus erythematosus. The mechanisms of self-tolerance affected by deficiency in either molecule are not established, but CD95 deficiency both in B cells and in CD4+ T cells recognizing major histocompatibility complex (MHC) class II molecules is required for autoimmunity in lpr mice. Here we track the outcome of in vivo interactions between B cells and CD4+ T cells that recognize a transgene-encoded autoantigen, hen egg lysozyme (HEL), using cells from mice transgenic for immunoglobulin and T-cell receptor (TCR) genes. B cells that had not previously encountered HEL autoantigen (naive cells) were triggered into proliferation and antibody production upon interaction with antigen and HEL-specific CD4+ T cells. By contrast, B cells that had been chronically exposed to HEL during their development and carried desensitized surface immunoglobulin (sIg) antigen receptors (anergic cells) did not produce antibody but instead were eliminated in the presence of HEL-specific CD4+ T cells. CD95-deficient anergic B cells, however, were not eliminated by CD4+ T cells and were triggered to proliferate. These findings identify a novel regulatory step for eliminating autoreactive B cells that seems unique in its dependence on CD95.
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PMID:CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ T cells. 760 71

CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently presented as peptide-MHC class II complexes when they are expressed as fusion proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusion proteins were associated intracellularly with MHC molecules. Most efficient expression of endogenous peptide-MHC complex was obtained with fusion proteins that contained the endosomal targeting signal within the N-terminal cytoplasmic Ii residues but did not require the luminal residues of Ii that are known to bind MHC molecules. These results suggest that signals within the Ii can allow endogenously synthesized proteins to efficiently enter the MHC class II presentation pathway. They also suggest a strategy for identifying unknown antigens presented by MHC class II molecules.
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PMID:Expression of endogenous peptide-major histocompatibility complex class II complexes derived from invariant chain-antigen fusion proteins. 763 70


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