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)

C57BL/10 mice exhibit major histocompatibility complex linked nonresponsiveness to hen egg white lysozyme (HEL). When these animals are primed with HEL in Freund's complete adjuvant (FCA), their secondary splenic plaque forming cell responses to aqueous HEL challenge are minimal to nonexistent. This notwithstanding, we show here that concomitant priming with both HEL and keyhole limpet hemocyanin (KLH) leads to an enhanced response to the HEL component following secondary challenge with an HEL-KLH conjugate. This enhancing effect can be transferred by nylon wool nonadherent spleen cells from HEL/FCA primed animals. Adoptive transfer studies with fractionated spleen cell populations suggest also that B cells are primed in these animals. Thus, animals which are incapable of mounting a secondary response to this antigen nevertheless appear to be primed at both the T-cell and B-cell levels following exposure to the antigen in FCA. The implications of this finding are discussed.
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PMID:Induction of latent immunological memory in genetically nonresponsive mice. 295

The present study tests whether the specific inhibition of helper T (Th) cell (and T hybridomas) by suppressor T (Ts) cells is a phenotypic trait of Th cells correlating with their acquired specificity for antigen/major histocompatibility complex or a genotypic trait not related to selection of the T cell repertoire for antigen. To do this we took advantage of the fact that H-2d parental strains of mice commonly restrict recognition of chicken egg-white lysozyme to the L3 peptide (a.a. 105-129) and H-2b parental mice to the L2 peptide (a.a. 13-105). F1 hybrids of these strains display two subsets of lysozyme-reactive T cells, one for each parental phenotype. Using (B10 X B10.D2)F1 mice reconstituted with B10.D2 bone marrow, we were able to develop genetic H-2d T cell clones that could express an atypical specificity, that is L2/I-Ab. Clones of this type, like genetic H-2b, are also sensitive to the inhibiting effects of HEL-activated Ts cells. To overcome some of the drawbacks of using heterogeneous populations of T, B and accessory cells in our assays, we constructed T hybridomas from HEL-immune, chimeric lymph node T cell blasts which respond to a unique antigen/major histocompatibility complex with production of the lymphokine interleukin 2. Our results indicate that all HEL/I-Ab-specific T cells (helper and hybridomas) are inhibited by suppression regardless of the T cell's haplotype at the H-2 locus: H-2b (B10), H-2d (D2) or H-2b,d (BDF1). Furthermore, there is a strict correlation between the antigen and I-A specificity: I-Ab-restricted T cells recognize non-L3 determinants even though some are derived from H-2d mice.
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PMID:An adjunct trait of HEL/I-Ab-specific T helper cell is sensitivity to antigen-specific immunosuppression. 296 40

We report the results of a phase I study of the tolerance and biologic activity of intramuscularly (IM)-administered recombinant interferon-gamma (rIFN-gamma). Forty-four patients with metastatic cancer were given rIFN-gamma at doses ranging from 0.01 to 2.5 mg/m2/d for 42 days. The most common side effects were fever, flulike symptoms, night sweats, and granulocytopenia. The maximum tolerated dose was 0.5 mg/m2/d. Administration of rIFN-gamma resulted in modulation of immune system functions, including induction of major histocompatibility complex-associated antigens on blood leukocytes, an increase in blood surface immunoglobulin-bearing B cell and natural killer (NK) cell number, and NK cell cytotoxicity. Serum lysozyme, determined as an estimate of tissue macrophage activity, also increased. Serum assays for anti-interferon antibodies were negative in all patients. Five of eight evaluable patients with lymphoproliferative disorders showed objective evidence of tumor regression consisting of partial responses (two patients), and minor responses (three patients). These data suggest that further phase II studies of IM-administered rIFN-gamma are indicated.
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PMID:Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. 308 21

Cytotoxic and helper T lymphocytes recognize foreign antigen in the form of short peptides associated with class I and class II major histocompatibility complex (MHC) molecules, respectively. A recent study of the three-dimensional structure of a class I MHC molecule revealed a cleft formed by the amino-terminal half of the protein, which could serve as the binding site for these peptides. Because an individual possesses only a limited set of different MHC molecules, each molecule of this set must have the ability to bind a large number of different peptides in order to ensure full immunocompetence. Thus, it can be anticipated that peptides with unrelated sequences compete for binding to the same MHC molecule, and, indeed, this has been shown to occur in vitro. We therefore decided to see whether such competition could also regulate the cell responses in vivo. We have found that a synthetic peptide corresponding to residues 46-62 of mouse lysozyme, although not immunogenic itself, effectively inhibits the priming for T-cell responses when injected into mice together with foreign protein or peptide antigens. The inhibition observed strictly correlates with the capacity of the competitor to bind to the particular MHC molecule presenting the foreign antigen, and its extent depends on the molar ratio between antigen and competitor.
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PMID:In vivo competition between self peptides and foreign antigens in T-cell activation. 326 93

The properties of rat liver dendritic cells (DC) were analyzed after collagenase digestion of the tissue and enrichment with density gradient centrifugation. The liver macrophages (Kupffer cells) were eliminated by adherence before the gradient centrifugation. The morphology of isolated DC in May-Grunwald-Giemsa (MGG) stained cytocentrifuge preparations resembled that of monocytes with certain dissimilarities. The expression of major histocompatibility complex (MHC) class II antigens (Ia) on DC was analyzed with the Staphylococcus aureus rosette method using a monoclonal antibody. The binding of anti-Ia antibody to rat liver DC was 3 times stronger than to passenger lymphocytes and 10 times stronger than to hepatocytes. All DC were Ia-positive tested with indirect immunofluorescence technique, and none of them were able to phagocytize antibody-coated human red cells. The DC did not express intracytoplasmic lysozyme, or surface Fc-receptors, and they all were negative in alpha-naphtylacetate esterase (ANAE) staining. Thus, although the dendritic cells of rat liver seem to belong to the monocytic series according to morphologic criteria, they were all negative when tested for typical monocyte/macrophage markers. The immunocenic potential of DC was analyzed by testing their ability to prime a naive recipient for graft rejection. The number DC needed for the priming was comparable with the number of spleen lymphocytes needed for an equivalent effect, indicating that the DC were highly immunogenic. The hepatocytes showed practically no immunogenic effect. Thus the immunogenic potential of the tested cells, i.e. their ability to induce accelerated transplant rejection, carries a good correlation with the expression of Ia-antigens on the cell surface.
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PMID:Characteristics of dendritic cells in rat liver. 328 40

The binding of 125I-labeled immunogenic peptides to purified Ia molecules in detergent solution was examined by equilibrium dialysis. We used the chicken ovalbumin peptide ovalbumin-(323-339)-Tyr, which is immunogenic in the BALB/c mouse and restricted to I-Ad. 125I-labeled ovalbumin-(323-339)-Tyr was shown to bind to I-Ad but not to I-Ed, I-Ek, or I-Ak. This binding was inhibited by unlabeled ovalbumin-(323-339) but not by ovalbumin-(329-339), which is the longest N-terminally truncated peptide that fails to stimulate any of the I-Ad-restricted hybridomas that have been raised to ovalbumin-(323-339)-Tyr. As a further specificity control, we also used the chicken egg lysozyme peptide Tyr-(46-61), which has recently been studied by similar methods [Babbitt, B. P., Allen, P. M., Matsueda, G., Haber, E. & Unanue, E. R. (1985) Nature (London) 317, 359-361]. We have confirmed that it bound to I-Ak but not to I-Ek, I-Ad, or I-Ed. Thus, a specific interaction between Ia and antigen that correlates with the major histocompatibility complex restriction was demonstrated, strongly arguing in favor of a determinant selection hypothesis for such restriction.
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PMID:Interaction between a "processed" ovalbumin peptide and Ia molecules. 348 84

Genes of the major histocompatibility complex (MHC) in the mouse (H-2 complex) have been shown to be an important factor in determining the immune responsiveness of various strains of mice to isolated antigens (e.g., lysozyme). The role of MHC genes in controlling the responsiveness of mice to multiple alloantigens is less well-defined, and although non-MHC genes have been shown to be important in determining responsiveness in some systems (e.g., haptens), they have not been demonstrated as yet to influence the rejection of vascularized organ allografts. In this study, the responsiveness of mice to vascularized cardiac allografts transplanted across well-defined major (H-2) and minor (non-H-2) histocompatibility barriers was investigated using congenic mice in 32 different donor/recipient combinations. The results show that both H-2 and non H-2 gene products can act as target alloantigens for rejection. At the responder level, they may interact to effect responsiveness of a recipient strain to multiple alloantigens. In no case in this study has any one gene or group of genes been found to confer universal high or low responder status.
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PMID:The role of H-2 and non-H-2 antigens and genes in the rejection of murine cardiac allografts. 351 Sep 70

We studied the antigen-presenting capacity of mouse L fibroblasts transfected with genes encoding Ia polypeptides of the major histocompatibility complex (MHC). These cells function as efficient antigen-presenting cells (APC) in stimulating peptide antigen-specific MHC-restricted proliferation of long-term T-cell lines, thus establishing the capacity of Ia-expressing L-cell transfectants to present antigens to apparently normal T cells. However, in contrast to splenic APC, L-cell transfectants fail to present native hen egg-white lysozyme to the same T cells. Since this result is similar to that obtained with physiologic APC pretreated to prevent antigen degradation, it suggests that L-cell transfectants, without such pretreatments, may be compromised in their ability to process native lysozyme. However, since such transfectant cells have been shown to present other complex polypeptides such as keyhole limpet hemocyanin, a random copolymer of glutamic acid, alanine, and tyrosine, and influenza virus neuraminidase, this observation suggests that protein antigens differ in the stringency of processing requirements.
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PMID:Ia-transfected L-cell fibroblasts present a lysozyme peptide but not the native protein to lysozyme-specific T cells. 387 53

The breadth of the expressed T cell repertoire to antigens under Ir gene regulation is central to the understanding of Ir gene function. While major histocompatibility complex (MHC)-related differences in the elicited T cell repertoire are readily demonstrated, the reasons for the choice of particular determinants are not clear. It is commonly assumed that the Ia molecules as the sole products of Ir genes somehow influence the choice of determinants selected for response. That this choice can be severely restricted in the C57BL/6 mice to hen egg-white lysozyme (HEL) was shown earlier with L2 (a.a. 13-105) immunization. L2, as the major cyanogen bromide cleavage fragment of HEL represents about 70% of the whole molecule and contains all the determinants recognize by proliferative T cells induced with HEL in this strain. All clones obtained from L2-immunized B6 mice recognized HEL and determinants available only within the T11 peptide (a.a. 74-96), suggesting that the entire T cell repertoire was restricted to determinants within the T11 region for HEL [1]. To test this hypothesis, long-term T cell lines were derived from HEL-immunized B6 mice. Bulk HEL- and L2-induced T cell lines showed similar L2-specific responses. However, in contrast to clones from the L2-lines, which were all specific for T11, the large majority of clones from the HEL-induced lines were specific for "non-T11" determinants. Antigen recognition of all clones was restricted by a similar restriction element on the I-Ab molecule. Thus, T cells directed against "non-T11" determinants available on the L2 fragment were not induced by L2 itself but required the whole molecule. The evidence clearly shows that within the T cell repertoire, the selection of clones is dramatically changed by the context in which the determinants are available. In fact, a hierarchy of T cells specific for T11 and "non-T11" determinants results. Structural differences between HEL and L2 lead to an inversion of this hierarchy. As both the HEL- and L2-induced lines were maintained and cloned under identical conditions, this appears to reflect the cellular interplay that occurs during the early in vivo selection period, rather than during the later in vitro activation and propagation of the lines and clones derived from them. The direct implications of these findings relate to interpretations of Ir gene phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen. 608 45

The lysozyme system provides an excellent model for studying the role of multiple major histocompatibility complex (MHC) genes in the induction and regulation of Ir-gene controlled immune responses. Immunization of H-2b mice leads to concomitant activation of helper and suppressor activities by different epitopes on hen egg-white lysozyme (HEL) and thus phenotype unresponsiveness to native HEL. HEL-specific suppressor T cells in C57BL/10 nonresponder mice show MHC restriction, because their enrichment on antigen-pulsed macrophage monolayers requires syngeneic macrophages as well as HEL. The expression of the selected suppressor function requires interaction between the restricted suppressor precursor cell and an HEL-triggered, suppressor-inducer T cell. The MHC-restricted suppressor precursors bear the predominant idiotype found on anti-HEL antibodies, whereas MHC-restricted helpers do not.
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PMID:Positive selection of major histocompatibility complex-restricted suppressor T cells bearing the predominant idiotype in the immune response to lysozyme. 616 94


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