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)

Hen egg white lysozyme (HEL)-specific T cell lines and clones were generated from B6 and BDF1 mice. A variety of clonotypes were found among clones generated at an early stage (1 month) whereas fewer clonotypes were detected after several weeks of culture. Furthermore, a bulk line switched from its initial fine peptide specificity pattern (positive for fragment L2--aa. 13-105--and negative for fragment NC--aa. 1-17:Cys 6-Cys 127:120-129) to the opposite pattern (negative for L2 and positive for NC), indicating that in bulk lines, besides selection toward oligo- or monospecificity, clones previously silent can emerge after a period of time. Irrespective of early or late cloning, T cell clones could be isolated from three independent T cell lines from different mouse strains that were stimulated by either native or denatured HEL, but not both. Furthermore, 1 clone of 20 from a B6 line, 3 clones of 25 from a BDF1 line, and 1 T hybridoma clone of 10 of B10.A origin lost their capacity to respond to native HEL, yet continued to respond to reduced, carboxymethylated HEL or cyanogen bromide-cleaved, unreduced HEL. These results suggest that T cells may produce activation signals for efficient processing of native antigen.
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PMID:Isolation of lysozyme-specific T cell clones that discriminate between native and denatured antigen. 813 Dec 10

The self-mouse lysozyme peptide corresponding to residues 46-62 (ML46-62) binds to the major histocompatibility complex (MHC) class II molecules I-A(k) and it selectively inhibits, when coinjected with antigen, priming of I-A(k)-restricted, antigen-specific T cells. We demonstrate that administration of ML46-62 also inhibits in vivo antibody responses induced by I-A(k)-restricted T helper cells. ML46-62 is able to prevent the primary anti-hen egg white lysozyme (HEL) antibody response induced by the entire HEL molecule in B10.A(4R) mice, expressing only I-A(k) molecules, but not in mice of H-2d haplotype. ML46-62 also strongly decreases, in B10.A(4R) mice, the antibody response to ribonuclease A, a protein antigen unrelated to the MHC blocker, indicating that MHC blockade is the mechanism leading to inhibition of antibody response. This is further supported by the concomitant decrease, in vivo, of complex formation between immunodominant HEL peptides and I-A(k) molecules, preventing I-A(k)-restricted T cell induction. Administration of ML46-62 after antigen priming does not affect ongoing antibody responses, as expected from MHC blockade. A single injection of ML46-62 at the time of protein antigen priming precludes not only the primary, but also the secondary antibody response to a subsequent challenge with soluble protein, even when the challenge is performed several months after priming. Coinjection of antigen and MHC antagonist inhibits production of all antibody isotypes equally well, suggesting that MHC class II blockade affects both Th1- and Th2-type T helper cells. Therefore, these results indicate that administration of MHC class II-binding peptides can efficiently and selectively prevent the induction of T cell-dependent primary and secondary in vivo antibody responses by blocking antigen presentation to class II-restricted T helper cells.
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PMID:Selective immunosuppression by administration of major histocompatibility complex class II-binding peptides. II. Preventive inhibition of primary and secondary in vivo antibody responses. 847 15

A self-peptide containing amino acid residues 46-61 (NRGDQSTDYGIFQINSR) of mouse lysozyme (ML) (p46-61, which binds strongly to the A(k) molecule but does not bind to the E(k) molecule), can induce a strong proliferative T cell response in CBA/J mice (A[k], E[k]) but no response at all in B10.A(4R) and CBA/J mice. The critical residues within p46-59 are immunogenic in both B10.A(4R) and CBA/J mice. The critical residues within p46-61 reside between amino acid positions 51 and 59. T cells of B10.A(4R) mice primed with the truncated peptides in vivo cannot be restimulated by p46-61 in vitro. This suggests that T cell receptor (TCR) contact (epitopic) residue(s) flanking the minimal 51-59 determinant within p46-61 hinder the interaction of the p46-61/A(k) complex with the appropriate TCR(S), thereby causing a lack of proliferative T cell response in this mouse strain. Unlike B10.A(4R) mice, [B10.A(4R) x CBA/J]F1 mice responded vigorously to p46-61, suggesting that thymic APC of B10.A(4R) mice do not present a self ligand to T cells resulting in a p46-61-specific hole in the T cell repertoire in B10.A(4R) or the F1 mice. Moreover, APC from B10.A(4R) mice are capable of efficiently presenting p46-61 to peptide-specific T cell lines from CBA/J mice. The proliferative unresponsiveness of B10.A(4R) mice to p46-61 is not due to non-major histocompatibility complex genes because B10.A mice (A[k], E[k]) respond well to p46-61. Interestingly, B10.A(4R) mice can raise a good proliferative response to p46-61 (R61A) (in which the arginine residue at position 61 (R61L/F/N/K), indicating that R61 was indeed responsible for hindering the interaction of p46-61 with the appropriate TCR. Finally, chimeric mice [B10.A(4R)-->B10.A] responded vigorously to p46-61, suggesting that thymic antigen presentation environment of the B10.A mouse was critical for development of a p46-61-reactive T cell repertoire. Thus, we provide experimental demonstration of a novel mechanism for unresponsiveness to a self peptide, p46-61, in the B10.A(4R) mouse owing to hindrance: in this system it is the interaction between the available TCR and the A(k)/p46-61 complex, which is hindered by epitopic residue(s) within p46-61. We argue that besides possessing T cells that are hindered by R61 of p46-61, CBA/J and B10.A mice have developed an additional subset of T cells bearing TCRs which are not hinderable by R61, presumably through positive selection with peptides derived from class II E(k), or class I D(k)/D(d) molecules. These results have important implications in self tolerance, shaping of the T cell repertoire, and in defining susceptibility to autoimmunity.
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PMID:Unresponsiveness to a self-peptide of mouse lysozyme owing to hindrance of T cell receptor-major histocompatibility complex/peptide interaction caused by flanking epitopic residues. 862 65

Intravenous injection of bovine serum albumin (BSA) into the BSA/CFA-primed ICR mice specifically induced anaphylactic death within 1 h. The anaphylactic death could not be induced until day 8 after sensitization, and sensitization subsisted for more than 3 months. The response was dose dependent; mice challenged with BSA doses higher or equivalent to 25 microgram developed anaphylactic death. The intravenous route was more effective than the intraperitoneal one, while subcutaneous injection was ineffective. Antigen in any of complete Freund's adjuvant, incomplete Freund's adjuvant or aluminum hydroxide could sensitize the mice to develop anaphylactic death. The combination of antigen and the mouse strain or the gender of the mouse determined the susceptibility of the anaphylactic death. AKR, B10.BR, as well as ICR, strains were susceptible. Antigen of HoGG induced a higher mortality rate than that of GAT or lysozyme. Male mice were more susceptible than female ones. The BSA-induced anaphylactic death could be prevented by pretreating ICR mice with cyproheptadine (histamine and serotonin antagonist) or diphenhydramine (histamine antagonist) and ketanserin (serotonin antagonist). Intravenous injection of saline during anaphylaxis also protected the mice from death. Furthermore, immune serum could transfer the anaphylactic death, and heat (56 degrees C, 4 h) did not destroy its activity. The primary IgG subclass induced by GAT, HoGG or lysozyme was IgG1. There was no qualitative difference in the IgG subclass induced in different strains by different antigens. The IgE class of antibodies was not detectable. These results suggest that there is a non-IgE-mediated anaphylactic death which involves the release of histamine and serotonin that cause the increase of vasopermeability and fatal blood volume loss.
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PMID:Antigen-induced anaphylactic death in mice. 863 27

Graft-versus-host disease (GVHD) is a T-cell-mediated disease of transplanted donor T cells recognizing host alloantigens. Data presented in this report show, to our knowledge, for the first time that a synthetic copolymer of the amino acids L-Glu, L-Lys, L-Ala, and L-Tyr (molecular ratio, 1.9:6.0:4.7:1.0; Mr, 6000-8500) [corrected], termed GLAT, with promiscuous binding to multiple major histocompatibility complex class II alleles is capable of preventing lethal GVHD in the B10.D2 --> BALB/c model (both H-2d) across minor histocompatibility barriers. Administration of GLAT over a limited time after transplant significantly reduced the incidence, onset, and severity of disease. GLAT also improved long-term survival from lethal GVHD: 14/25 (56%) of experimental mice survived > 140 days after transplant compared to 2/26 of saline-treated or to 1/10 of hen egg lysozyme-treated control mice (P < 0.01). Long-term survivors were documented to be fully chimeric by PCR analysis of a polymorphic microsatellite region in the interleukin 1beta gene. In vitro, GLAT inhibited the mixed lymphocyte culture in a dose-dependent fashion across a variety of major barriers tested. Furthermore, GLAT inhibited the response of nylon wool-enriched T cells to syngeneic antigen-presenting cells presenting minor histocompatibility antigens. Prepulsing of the antigen-presenting cells with GLAT reduced the proliferative response, suggesting that GLAT inhibits antigen presentation.
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PMID:A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo. 864 29

The mouse Nramp1 (Bcg) gene on chromosome 1 exerts pleiotropic effects on macrophage function. The gene is known to affect presentation of mycobacteria, and other antigens in vitro, so that macrophages carrying the resistant Bcg allele better support the proliferation of antigen-specific T cells compared with macrophages of the sensitive phenotype. To determine whether the Bcg allele could affect in vivo the antibody response to antigens not related to mycobacterial infections, we tested the primary and secondary responses to sheep red blood cells (SRBC) and glycosylated bovine insulin (G-insulin) in two pairs of Bcg congenic strains: BALB/c (Bcgs) versus BALB/c.CD2 (Bcgr), and B10.A (Bcgs) versus B10Ar (Bcgr), and in C57BL/10ScSn (B10; Bcgs) and A/J (Bcgr) mice. Furthermore, the antigen-specific proliferative responses of T cells primed in vivo by protein antigens were also tested in Bcg congenic mice. We found no significant difference in in vivo antibody response either to SRBC or G-insulin between the Bcgr and Bcgs strains. The magnitude of in vitro antigen-specific proliferation of lymph node cells sensitized in vivo by hen egg lysozyme (HEL) or chicken ovalbumin (OVA) was also similar in Bcgs and Bcgr congenic mice. However, we have documented a higher antigen-presenting capacity of Bcgr macrophages in in vitro antigen-specific proliferation to OVA. Since the macrophages are the only cells in which the Nramp1 gene is expressed, we suggest that the activity of other types of antigen-presenting cells masks the effect of the Bcgr allele on antigen-presentation in vivo.
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PMID:The in vivo antibody response against exogenous antigens is not influenced by the mouse Bcg (Nramp1) gene. 917 18

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-gamma. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-gamma secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non-CpG ODN did not induce IFN-gamma or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.
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PMID:CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. 936 23

Hybrid F1 mice derived from inbred parental mouse strains are extensively used as animal models of human autoimmune diseases and transplantation. It is generally believed that with regard to immunologic studies, hybrid F1 mice behave in a consistent manner, equivalent to any other inbred mouse strain. In this study, we report that in comparison to inbred parental strains, individual hybrid F1 mice revealed a broad heterogeneity of proliferative response to the immunodominant determinants within hen eggwhite lysozyme (HEL). Of five parental strains tested, individual mice of three strains responding to only a few dominant HEL determinants (B6, BALB/c, and B10.PL) showed quite homogeneous patterns of response, whereas two mouse strains responsive to several determinants of HEL revealed either relative homogeneity (CBA/J mice) or heterogeneity (SJL mice) of response. However, in SJL mice, responses to major, dominant determinants of HEL were quite consistent. On the contrary, regardless of the consistency of response of parental strains, all three of F1 mice [[B6 x BALB/c]F1, [B6 x CBA/J]F1, and [SJL x B10.PL]F1] revealed significantly greater heterogeneity of response, which even involved the major, dominant determinants of HEL. We attribute the above heterogeneity of response to the competitive as well as aleatory nature of the interaction between various factors, including the coexistence of different MHC (parental as well as hybrid MHC) molecules, determinant capture, and the T cell repertoire. These results have important implications for studies on autoimmunity, infection, and vaccine design in human populations, where heterozygosity is the norm rather than the exception.
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PMID:Heterogeneity of the T cell response to immunodominant determinants within hen eggwhite lysozyme of individual syngeneic hybrid F1 mice: implications for autoimmunity and infection. 983 87

Infections with parasitic helminths such as Nippostronglyus brasiliensis induce dominant type 2 responses from antigen-specific T helper cells. The potency of the Th2 bias can also drive Th2 responses to bystander antigens introduced at the same time as infection. We now report that the Th2-promoting effect of infection can be reproduced with soluble N. brasiliensis excretory-secretory proteins (NES) released by adult parasites in vitro. Immunization of BALB/c mice with NES results in the production of IL-4 with elevated total serum IgE and specific IgG1 antibodies. NES is also able to stimulate IL-4 and polyclonal IgE production in other mouse strains (C57BL/6, B10.D2, CBA). These features are seen whether NES is administered without adjuvant as soluble protein in phosphate-buffered saline or with complete Freund's adjuvant which normally favors Th1 responses. Thus, NES possesses intrinsic adjuvanticity. Moreover, co-administration of hen egg lysozyme (HEL) with NES in the absence of other adjuvants results in generation of HEL-specific lymphocyte proliferation, IL-4 release and IgG1 antibody responses, documenting that NES can act as an adjuvant for third-party antigens. Proteinase K digestion or heat treatment of NES before immunization abolished the IL-4-stimulating activity, indicating that the factors acting to promote Th2 induction are proteins secreted by the adult parasite.
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PMID:Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. 1094 Aug 87

We determined if a single amino acid substitution in a self protein causes autoantibody responses. Mouse lysozyme (ML) was used as a model self protein, and a mutant ML (F57L ML) was prepared by replacing 57Phe of ML to Leu, an approach which resulted in introducing into ML the immunogenic sequence of peptide 50-61 of hen egg lysozyme (HEL) restricted to I-A(k) MHC class II molecule. We found that F57L ML but not native ML primed HEL specific T cells and triggered ML specific autoantibody responses in B10.A and C3H mice (I-A(k), I-E(k)). Peptide regions, ML 14-69 and ML 98-130, were major epitopes of autoantibodies in both strains of mice. These findings indicate that a single amino acid substitution in self proteins can cause an autoantibody response when the mutated region is presented by MHC class II molecules and recognized by T cells.
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PMID:A single amino acid substitution in a self protein is sufficient to trigger autoantibody response. 1168 93


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