Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.65 (Der p 1)
 346 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that intranasal (i.n.) administration of an immunodominant peptide (p1-111-139) derived from the house dust mite (HDM) allergen Der p 1 inhibits antigen-specific CD4+ T cell responses in H-2b mice. Here we report that i.n. peptide induced a rapid but transient activation of MHC class II restricted CD4+ T cells that peaked 4 days after peptide treatment and was of similar magnitude to that induced by parenteral immunization with antigen in adjuvant. During the early phase of the response lymph node and splenic T cells secreted a range of lymphokines when re-stimulated in vitro with p1 111-139; however, by day 14 IL-2 and IFN-gamma secretion by T cells were down-regulated. Mice deficient in CD8+ T cells became tolerant by i.n. treatment with peptide, suggesting that CD8+ T cells are not involved in down-regulating the CD4+ T cell response. Rechallenging mice with a single dose of p1 111-139 21 days after the initial treatment elicited a further transient T cell response, which was subsequently down-regulated over time. Although the i.n. peptide induced a strong transient CD4+ T cell response, only low levels of peptide-specific antibodies were detected either after the initial or subsequent i.n. exposures to p1 111-139. Our findings address the mechanisms underlying peripheral T cell tolerance following i.n. administration of a high dose of immunogenic peptide and have implications for understanding the consequences of peptide immunothearapy.
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PMID:Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. 867 19

In this study we demonstrate that immunization of H-2(b) mice with the allergen Der p 1 induces MHC class II restricted T cells that proliferate to residues 15-29 of Der p 1 (p15-29) and to the murine MHC class II-associated invariant chain derived peptide (CLIP). T cells from naive H-2(b) mice and those immunized with murine CLIP fail to respond to either CLIP or p15-29. T cell lines and clones reactive with p15-29 strongly proliferate in response to splenic antigen-presenting cells (APC) from normal H-2(b) mice but show reduced proliferation to APC from invariant chain deficient mice. Furthermore, T cells isolated from Der p 1 primed mice and expanded on H-2(b) spleen cells in the absence of the p15-29 epitope retained specificity for both p15-29 and CLIP, suggesting that naturally presented self components can act as mimetic peptides and may maintain T cell memory to foreign antigens.
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PMID:Induction of T cell responses to the invariant chain derived peptide CLIP in mice immunized with the group 1 allergen of house dust mite. 875 54

Allergic inflammatory responses are regulated by cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] produced by CD4+ helper (Th0 and Th2) cells. The activation of these T cells follows engagement of T-cell antigen receptors (TCR) by antigenic peptides complexed with major histocompatibility complex (MHC) class II molecules. Under defined conditions presentation of T-cell epitopes as peptides can downregulate immune responses, and here we discuss the potential of peptide-mediated immunotherapy in the regulation of responses to the house dust mite (HDM). Cloning the major allergens of HDM has allowed detailed analysis of the HDM-reactive T-cell repertoire and has revealed that MHC class II restriction is heterogeneous, involving HLA-DP,-DQ, and -DR molecules, and that multiple T-cell epitopes are recognized. There is, however, evidence for a bias in TCR gene usage, which has prompted the analysis of peptide-mediated densitization of human T cells in vitro. CD4+ T cells exposed to high concentrations of HDM peptides become refractory to restimulation and fail to provide B-cell help. This is accompanied by complex changes in the surface phenotype, including the downregulation of TCR and CD28. During the induction of anergy cytokine-specific mRNA levels are enhanced, but when the anergic T cells are restimulated they fail to secrete IL-4 and IL-5, although interferon (IFN)-gamma production may remain unaltered. The ability of peptides to modulate the function of HDM-specific T cells in vivo has been investigated in mice. Following inhalation of peptide containing a major T-cell epitope of Der p 1 (residues 111-139) transient T-cell activation was observed prior to the inhibition of responses in naive and sensitized mice. T cells from the tolerant mice restimulated in vitro produced low levels of cytokines and failed to provide help for B cells.
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PMID:From epitopes to peptides to immunotherapy. 881 Oct 60

The group I (Der p 1) allergen of Dermatophagoides pteronyssinus (house dust mite, HDM) contains several T helper (Th) epitopes recognized by C57BL/6 mice, with the peptide (111-139) containing a dominant MHC class II-restricted epitope (113-127). Since CD8+ T cells are thought to play a role in the regulation of allergic disease, we examined the Der p 1 sequence for potential MHC class I-binding motifs and observed that residues 111-119 (FGISNYCQI) contain motifs for H-2Db and Kb. Furthermore, immunization of C57BL/6 mice with unadjuvanted Ty virus-like particles (VLP) carrying Der p 1 (111-139), a method known to induce murine cytotoxic T lymphocyte (CTL) responses, primed Der p 1 (111-119)-specific Db-restricted CTL which produce high levels of IFN-gamma and low levels of IL-5 and IL-6 in vitro (T1-type CTL). VLP carrying the minimal epitope (FGISNYCQI) also induced a CTL response following immunization without adjuvant by various routes. Der p 1 (111-139)-VLP adjuvanted with alum did not prime CTL in C57BL/6 mice but were found to prime Th1-type CD4+ T cells that recognize the overlapping peptide (113-127) and native protein. The ability to successfully predict allergen-specific CD8+ T cell epitopes and prime CD8+ and/or CD4+ T cell responses provides an opportunity to dissect the relative roles of these T cells in the regulation of allergic responses and may offer therapeutic potential for reprogramming Th2-type allergic responses.
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PMID:Prediction of murine MHC class I epitopes in a major house dust mite allergen and induction of T1-type CD8+ T cell responses. 904 9