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 role of non-H-2 gene(s) in the control of the antibody response to three lysozymes was investigated. Upon secondary challenge, A/J (H-2a) mice generated at least a 25-fold greater anti-lysozyme plaque-forming cell response than did B10.A (H-2a) mice. Nearly equal, strong peak primary responses, predominantly IgG in nature, were obtained from both A/J and B10.A mice after a single challenge with lysozyme in complete Freund's adjuvant. However, clear differences in responses are seen within 5 days after the peak primary plaque-forming response and by day 28 at the serum antibody level. B10.A mice never equal their primary responses, whereas A/J mice demonstrate positive immune memory. It appears that a non-H-2 gene(s) that regulates the overall antibody level to a protein antigen becomes manifest only after an initial antibody response.
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PMID:Delayed advent of stringent, non-H-2 genetic regulation of the antibody response to a protein antigen. 38 37

The specificity of lysozyme-induced T cell proliferative responses by individual B10.A mice was compared by using a panel of three peptides. A surprising degree of variation in the focus of the responses was observed among individual animals, both in the newly isolated lymph node cell populations and in long term T cell lines. The responses to each determinant after hen egg-white lysozyme immunization were not equal and in examining the mice as a group some determinants tended to be dominant. However, despite each animal favoring a restricted number of determinants, the responding T cell populations were still highly heterogeneous. The data suggest that many determinants are involved in the response to the whole Ag. The role of one or more dominant determinants can be overestimated because the degree of heterogeneity in long term T cell lines appears to be less than in freshly obtained lymph node cells, indicating that a process of in vitro selection occurs. We observed that the T cells responsive to one peptide, 46-61, appeared to have a selective advantage in vitro culture.
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PMID:The T cell repertoire to a multideterminant antigen. Clonal heterogeneity of the T cell response, variation between syngeneic individuals, and in vitro selection of T cell specificities. 168 49

The specificity of C57BL/6 T cells reactive to peptide aa 74-96 of hen egg-white lysozyme (HEL) was analyzed by using a panel of synthetic peptides of varying lengths from this region. It was found that peptide 74-96-reactive T cells induced by native HEL (aa 1-129) or its denatured fragment L2 (aa 13-105) recognized two distinct but overlapping determinants contained within aa 74-90 or aa 81-96, respectively. Peptide 74-96 itself induced both peptide 74-90-and peptide 81-96-specific T cells. Thus, a choice was made between these two potential T cell determinants on peptide 74-96, depending on which immunogen was used. Interestingly, the ability of both peptide determinants aa 74-90 and aa 81-96 to stimulate peptide 74-96-reactive T cells was partly dependent on the presence of residues within the overlap region (aa 81-90), suggesting that this region may play an important role in Iab-restricted T cell activation. This was further supported by the poor immunogenicity of shorter peptides 74-86 or 85-96, lacking residues from the overlap region in B6 mice. These two short peptides were nevertheless capable of eliciting T cell responses in B10.A mice, suggesting that the importance of this overlap region in obtaining a response to peptide 74-96 is related to the MHC haplotype.
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PMID:The choice between two distinct T cell determinants within a 23-amino acid region of lysozyme depends on their structural context. 242 89

Ak- or Ek-restricted T cells, generated by immunization with a 23-amino-acid peptide of hen egg-white lysozyme (amino acid 74-96), showed a strict correlation between the minimal peptide determinant recognized and the Ia molecule restricting recognition. All Ak-restricted clones obtained from six independently derived lines recognized determinants contained within peptides 74-86, while Ek-restricted clones recognized determinants within 85-96. This correlation was true whether B10.A mice (Ak, Ek) were immunized with peptide 74-96 or with each of the two smaller peptides (74-86 or 85-96). Furthermore, a T cell response could be obtained to peptide 74-86, but not to peptide 85-96 in B10.A (4R) mice, which express only the Ak molecule. Thus, an Ia molecule-associated selectivity exists in the choice of T cell determinants even within this small 23-amino-acid peptide antigen. Significant differences were noted, however, in the boundaries of the minimal peptide determinants recognized within peptide 74-96 by Ak- or Ek-restricted T cells, in comparison to those recognized by Ab-restricted T cells. These results indicate that interaction of the same peptide with distinct Ia molecules results in recognition of unique aspects of the antigenic determinants by the T cell receptor.
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PMID:Ia molecule-associated selectivity in T cell recognition of a 23-amino-acid peptide of lysozyme. 242 37

Presentation of a protein antigen to T cells is believed to follow its intracellular breakdown by the antigen-presenting cell, with the fragments constituting the trigger of immune recognition. It should then be expected that T-cell recognition of protein antigens in vitro will be independent of protein conformation. Three T-cell lines were made by passage in vitro with native lysozyme of T cells from two mouse strains (B10.BR and DBA/1) that had been primed with the same protein. These cell lines responded well to native lysozyme and very poorly to unfolded (S-sulphopropyl) lysozyme. The response of the T-cell lines to the antigen was major histocompatibility complex (MHC)-restricted. A line from B10.BR was selected for further studies. This line responded to the three surface-simulation synthetic sites of lysozyme (representing the discontinuous antigenic, i.e. antibody binding, sites) and analogues that were extended to a uniform size by a nonsense sequence. T-cell clones prepared from this line were specific to native lysozyme and did not respond to the unfolded derivative. Furthermore, several of these clones showed specificity to a given surface-simulation synthetic site. The exquisite dependency of the recognition by the clones on the conformation of the protein antigen and their ability to recognize the surface-simulation synthetic sites indicate that the native (unprocessed) protein was the trigger of MHC-restricted T-cell recognition.
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PMID:Conformation-dependent recognition of a protein by T cells requires presentation without processing. 247 11

Whether T cell tolerance represents direct inactivation of antigen-specific T cells via recognition of antigen plus major histocompatibility complex, or via T suppressor (Ts) cells, or a combination of these mechanisms, remains to be clarified. This problem was investigated using a novel approach based on the finding in several systems that T helper/proliferative (Th/Tp) cell-inducing antigenic determinants are dissociable from Ts cell-inducing determinants. Thus, peptide probes containing known sites that stimulate T proliferative activity, as well as peptides from distinct sites assumed to bear Ts-inducing determinants, were used in studying hen (chicken) eggwhite lysozyme (HEL)-tolerant mice. The clear prediction from clonal deletion model is that Th/Tp response potential to short peptides in the tolerant mouse would not exist, while regulatory suppression models predict the coexistence of antigen-reactive cells and antigen-specific regulatory cells that prevent their expression. Adult mice, treated with 2 mg HEL in saline, were tolerant to HEL in complete Freund's adjuvant (CFA). Latent T cell proliferative responses could be revealed to determinants within two HEL peptide probes, which lacked the amino-terminal region of the molecule. This responsiveness suggested two conclusions: first, Ts cells directed against the amino terminus of lysozyme exist in the tolerant genetic responder B10.A; second, these Ts regulate the activity of functional antigen-reactive T cells directed against epitopes elsewhere on the molecule, but only in the presence of the complete molecule, HEL. Examination of neonatally induced tolerance did not reveal any latent responsiveness, supporting the hypothesis that clonal deletion or anergy is the relevant mechanism in this situation. Possible reservations in these explanations of the two tolerant states, plus analysis of the more complex "split tolerance" resulting from 20 mg HEL in saline treatment in adults, are discussed. The approach of dissociation of proliferation-inducing determinants from suppression-inducing determinants clarifies our understanding of the tolerant state and holds promise for more definitive exploration of mechanisms of T cell tolerance.
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PMID:T cell tolerance studied at the level of antigenic determinants. I. Latent reactivity to lysozyme peptides that lack suppressogenic epitopes can be revealed in lysozyme-tolerant mice. 258 Sep 37

Immune responsiveness to lysozyme in H-2b mice is under the control of H-2-linked Ir genes, with T suppressor (Ts) cells playing a dominant role in strains such as C57BL/6 (B6), C57BL/10 and A.BY. However, non-H-2-genes were found to be capable of specific reversal of the effect of the H-2-linked genes in responsiveness to chicken lysozyme (HEL), but not to human lysozyme (HUL). Therefore, studies were performed to identify any lesion in the suppressor circuit in BALB.B. It was known that HUL-induced suppressor cells could cross-suppress the anti-HEL response in B10.Q mice, which are responsive to HEL but nonresponsive to HUL. Similarly, BALB.B Ts cells were able to suppress the anti-HEL response, using as T helper (Th) source a T cell line (BB-1), derived from HEL-primed BALB.B periaortic and inguinal lymph node cells. A protocol designed to examine the in vivo suppression by the use of HUL-induced suppressor cells also demonstrated a significant suppression of the anti-HEL response. Since the suppressive circuitry seemed intact in the BALB.B, the possibility was examined that a step in T-B cell collaboration was more efficient in this strain than in the B6 nonresponder. With a B6-derived HEL-specific T cell line, BO1H, the B cell and antigen-presenting (B/APC) populations from B6 required addition of concanavalin A supernatant for anti-HEL antibody formation, whereas BALB.B B/APC were capable of responding to HEL in culture without the addition of concanavalin A supernatant. In agreement with this finding, when B/APC cell populations from BALB.B and B6 were compared for their extent of anti-HEL responsiveness, as measured with BB-1 Th cells, BALB.B B/APC populations responded significantly higher than B6 populations when the responses were activated by picogram/nanogram amounts of HEL. The response level of (BALB.B X B6)F1 B/APC measured in the same assay resembled that of B6. However, when HEL was used at the microgram level, both B6 and BALB.B strains responded equivalently. The above data are consistent with the expression of the reversing non-H-2 Ir gene(s) resulting from the balance of antigen presentation to Th and Ts cells in the H-2b mouse. In the B6, processing and handling of antigen may be inefficient in activating response-enhancing Th, and more effective in triggering Ts cells, while the reverse may be true for the BALB.B.
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PMID:Selective reversal of H-2-linked genetic unresponsiveness to lysozymes. II. Alteration in the T helper/T suppressor balance, owing to gene(s) linked to Ir-2, leads to responsiveness in BALB.B. 293 74

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

Recently, this laboratory has developed a comprehensive strategy for the systematic localization of all the 'continuous' antigenic (as well as other binding) sites of complex multivalent protein antigens involved in B and T cell recognition. The strategy depends on the synthesis of consecutive overlapping peptides that together account for the entire protein chain. This strategy was applied here for the localization of the 'continuous' T cell recognition sites of hen egg lysozyme. Eight overlapping peptides encompassing the entire protein chain of lysozyme were synthesized and examined for their ability to stimulate in vitro proliferation of T cells from several mouse strains (A/J, H-2a; BALB/c and DBA/2, H-2d; B10.BR, H-2k; DBA/1, H-2q; SJL, H-2s) that had been primed with native lysozyme. This approach enabled the identification of a full profile of in vitro active lysozyme peptides and the localization of four major T cell recognition sites, three of which were subject to individual control.
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PMID:T cell recognition of lysozyme. IV. Localization and genetic control of the continuous T cell recognition sites by synthetic overlapping peptides representing the entire protein chain. 608 92

B10 mice, although genetically nonresponsive to hen egg-white lysozyme (HEL) after i.p. immunization due to suppressor T cells, make a vigorous helper and proliferative T cell response in the draining popliteal lymph nodes (P-LN) soon after footpad immunization with HEL. The fundamental specificity repertoire in B10 P-LN analyzed with cross-reactive lysozymes, was then compared with that found after the delayed appearance of suppression, in the PETLES. In contrast with B10.A mice, whose T cell specificity pattern was unchanged with time, or anatomical site, the onset of HEL-induced suppression in B10 mice led to a marked heteroreactive shift in specificity pattern. This shift did not occur after immunization with REL (ring-necked pheasant lysozyme), which fails to induce suppression.
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PMID:The fundamental T cell proliferative repertoire in a nonresponder strain and its qualitative alteration by suppression. 615 93


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