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)

The gallinaceous lysozymes are a family of antigens that are distantly related to mouse lysozyme. A T cell-dependent proliferation assay was used to characterize the spectrum of reactivities to lysozyme determinants in B10-congenic mice. Cross-reactivity studies using a panel of species variant lysozymes to stimulate lymph node cells from chicken egg white lysozyme- and ring-necked pheasant egg white lysozyme-primed B10.D2 mice indicated a preferential focusing of T cell reactivity onto a single determinant containing amino acids 113-114. These data, in conjunction with results obtained by priming with cyanogen bromide cleavage fragments of lysozymes, suggested that a site commmon to the L3 region (amino acids 106-129) of all the lysozymes tested was a preferential anchorage site for I region-encoded Ia molecules on H-2d antigen-presenting cells, leading to the limited display of a determinant containing residues 113-114. Priming with L2H (amino acids 13-105), a peptide containing the major epitopes recognized by B10. A and B10 mice, failed to stimulate any T cell proliferation by B10.D2 lymph node cells. Thus, it appears the Ia molecules in any one mouse strain attach to very few sites on lysozyme to effectively display antigenic determinants for T cell activation. This result points to a model of limited determinant selection even on a very "foreign" antigen based upon a shortage of appropriate amino acid residues usable by Ia antigen-presenting structures of a strain.
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PMID:Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes. 618 Sep 5

Suppressor T cells (Ts) induced by lysozyme-modified syngeneic lymphocytes were characterized. Hen egg-white lysozyme (HEL)-specific delayed-type hypersensitivity (DTH) was suppressed when HEL-induced Ts were transferred into naive mice. These HEL-induced Ts had surface markers of both Thy-1 antigen, and I-J gene products. The suppression of HEL-specific DTH was greatly increased, when these Ts had been enriched with HEL-coated petri dishes. Isolated anti-HEL antibodies from B10.BR or A/Sn mice were inoculated into rabbits to induce anti-cross-reactive idiotype (CRI) antibodies. The rabbit antisera were extensively absorbed with normal B10.BR or A/Sn immunoglobulins (Igs) and MOPC 104E ascites Igs to render them idiotype (Id) specific. Using these anti-CRI antibodies, we observed that these Ts possessed Id receptors on their cell surface. Results of both fluorescence techniques and cytotoxicity tests revealed that about 10% of the enriched T cells containing these Ts were Id positive. Moreover, these enriched T cells were substantially killed by anti-I-J antiserum plus complement. However, this killing was completely blocked by HEL antigen. These results suggest that both Id receptors and I-J gene products might be forming the same molecular complexes or might coexist in the vicinity of the molecule.
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PMID:Delayed-type hypersensitivity to hen egg-white lysozyme. I. The surface phenotypes of suppressor T cells induced by intravenous injection of lysozyme-modified spleen cells, and their molecular interactions. 618 95

Recently, by using a comprehensive synthetic strategy developed in this laboratory, we localized four sites (T sites) within the polypeptide chain of lysozyme recognized by T cells from two high responder mouse strains, DBA/1 and B10.BR. However, to detect minor specificities, the selective enrichment of lysozyme reactive cells, would be required. T cells from long-term cultures maintained by repeated stimulation with antigen are selectively enriched for that antigen. It is not known whether maintaining T cells for extended periods of time in vitro has any consequences on the profile of T cell recognition. In the present study, T cells from long-term cultures, derived from these two high responder lysozyme-primed mouse strains, were examined for their responsiveness to a series of synthetic overlapping peptides encompassing the entire polypeptide chain of the lysozyme molecule. We have found that the profile of T cell recognition of the long-term cultures may not reflect that of the lysozyme primed lymph node cells, but that it is subject to a shift in specificity towards submolecular features of the molecule. In addition, we have identified in B10.BR mice another region within the polypeptide chain of lysozyme (residues 72-84) which may potentially harbor a previously undetected (in lymph node cells) minor T site.
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PMID:T cell recognition of lysozyme. II. Shift in specificity during long-term culture determined by synthetic overlapping peptides comprising the entire protein chain. 620 28

In previous studies from this laboratory the antigenic sites of lysozyme were found to be composed of spatially adjacent surface residues that are mostly distant in sequence (i.e. discontinuous sites). For synthetic mimicking of the sites, we introduced the concept of 'surface-simulation' synthesis by which the binding site residues are linked directly via peptide bonds with appropriate spacing and directionality into a single peptide which does not exist in the protein but mimics a surface region of it. In the present report T cell recognition of the surface-simulation synthetic antigenic sites has been explored in a mouse strain, B10.BR, that is a high responder to lysozyme. The discontinuous antigenic sites of lysozyme also had the capacity to stimulate proliferation of T cells driven by native lysozyme in long-term cultures. Thus, in addition to the four continuous T sites that we have recently reported, T cell recognition of lysozyme also involves discontinuous sites. This is the first clear demonstration that, contrary to a long-held impression, T cell recognition is not restricted only to sequence features, but can also be directed to protein discontinuous surface areas of high conformational dependency.
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PMID:T cell recognition of lysozyme. III. Recognition of the 'surface-simulation' synthetic antigenic sites. 633 54

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

B10 (H-2b) mice are genetic nonresponders to hen egg-white lysozyme (HEL) and the distantly related human lysozyme (HUL). However, anti-HEL or anti-HUL primary antibody responses in vivo or in vitro can be obtained in B10 mice by immunization with the appropriate lysozyme coupled to erythrocytes. T cells able to suppress either anti-lysozyme plaque-forming cells (PFC) response are induced in B10 mice after immunization with HEL-complete Freund's adjuvant (CFA) or HUL-CFA. This cross-reactivity of HEL and HUL in the induction and the expression of suppressive activity is in marked contrast to their very low cross-reactivity at the PFC level. These results suggest that either HEL or HUL can stimulate a suppressor T cell which recognizes a particular epitope present on both lysozymes. Suppressor cells induced by HEL or HUL bear the same predominant idiotype found on the majority of anti-HEL antibodies, and on the small proportion of anti-HUL antibodies cross-reactive with HEL. B10.Q (H-2q) mice are responders in vivo to HEL-CFA, but not to HUL-CFA. In contrast to B10, HEL-CFA priming in B10.Q micr induces helper cells whereas HUL-CFA priming induces suppressor cells. These suppressor cells are cross-reactive with HEL and are fully able to suppress HEL-specific helper cells. The presence of HEL-specific suppressor cell precursors in B10.Q mice which are not activated by HEL, seems to implicate differential choice by the antigen presenting system as a basis for Ir gene control, rather than the absence of a regulatory cell type from the T cell repertoire.
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PMID:Differential major histocompatibility complex-related activation of idiotypic suppressor T cells. Suppressor T cells cross-reactive to two distantly related lysozymes are not induced by one of them. 644 50

A method is described for the production of T-cell lines and clones specific for solubilized Trichinella spiralis antigens. These T cells are antigen-specific and do not respond to challenge with a third party antigen (lysozyme). The proliferation responses of the cloned T cells are specifically inhibited by anti-I-E but not by anti-I-A subregion monoclonal reagents. The inhibition patterns obtained are consistent with cis-gene complementation in B10.K cells involving the Ek beta-chain and the Ek alpha-chain of the I-E molecule. Inhibition is obtained with an Ek beta-specific monoclonal antibody (H9-14.8) but not with an Ak beta-specific monoclonal antibody (10-2.16). Inhibition was also observed with Ia.7-specific (H40-242) or Ia.22-specific (17-3-3) monoclonal antibodies. The inhibition patterns were confirmed by antigen presentation experiments using recombinant inbred mice. Only B10.K (Ek beta Ek alpha) spleen cells and not B10.A(5R) (Eb beta Ek alpha) or B10.S(9R) (Es beta Ek alpha) spleen cells could effectively present T. spiralis antigens. The role of "hybrid" Ia molecules in the immune response to T. spiralis is discussed.
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PMID:Cloned T cells recognize Trichinella spiralis antigen in association with an Ek beta Ek alpha restriction element. 660 15

A hen egg-white lysozyme-lipopolysaccharide complex (HEL-LPS) can stimulate an in vitro IgG response, but only from HEL-primed B lymphocytes; unprimed cells only produce an IgM response. These conditions were used to determine whether IgG memory B cells are cryptically induced in B10 nonresponder (H-2b) mice after an HEL injection protocol. The usual i.p. immunization that triggers IgG memory production in congenic responder strain mice fails to yield IgG in vitro from HEL-primed B10 spleen cells after stimulation with HEL-LPS. However, injection protocols immunogenic for B10 mice do engender IgG-memory cells. These results imply that the T helper cell population necessary for triggering B cells to the IgG memory stage cannot develop in the nonresponder mouse, presumably due to HEL-specific T suppressor cells.
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PMID:The failure of nonresponder mice to develop IgG memory assessed by in vitro culture with an antigen-LPS conjugate. 697

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

In this study, the major endosomal/lysosomal proteases cathepsin D and cathepsin B were tested on their ability to release T cell stimulatory peptides from hen egg white lysozyme (HEL) in vitro. Whereas neither enzyme could cleave unreduced HEL under mild conditions, reduced HEL was readily cleaved by cathepsin D but not by cathepsin B. Instead, cathepsin B was found to be very active in the trimming of HEL peptides after their release by cathepsin D. Following high-performance liquid chromatography (HPLC) fractionation, cathepsin D-released HEL fragments were screened for recognition by HEL-specific T cells from three strains of mice, i.e. B10.A (H-2a), C57BL/6 (H-2b) and BALB/c (H-2d). Peptides in a large number of different HPLC fractions triggered significant T cell responses in all three strains. Interestingly, the response profiles of T cells from the three different strains showed marked similarities. Also, several individual synthetic HEL sequences corresponding to selected cathepsin D-released fragments were recognized by murine T cells in the context of all three major histocompatibility complex (MHC) haplotypes tested. Our data suggest that cathepsin D rather than cathepsin B may play a central role in the initial release of HEL fragments during endosomal/lysosomal processing. The relatively long HEL fragments released by cathepsin D, containing about 20-30 amino acid residues, are significantly more promiscuous in murine class II MHC binding than the shorter synthetic HEL sequences previously employed by others for the delineation of HEL epitopes. Extensive documentation of HEL epitopes in previous investigations indicate that this promiscuity cannot be explained by simply assuming that longer peptides contain additional epitopes. Rather, an increased peptide length by itself appears to promote promiscuous MHC binding.
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PMID:Cathepsin D, but not cathepsin B, releases T cell stimulatory fragments from lysozyme that are functional in the context of multiple murine class II MHC molecules. 808 34


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