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)

From a community-based study cohort of 1812 elementary schoolchildren we selected 129 unrelated participants to investigate the relevance of HLA-class II molecules (DPB, DQB, and DRB) to the regulation of immune response to the mite allergen Der p 1 and to clinical atopic disorders. On the basis of skin prick test results validated by measurement of specific IgE, individuals were selected and divided into three groups: group I (n = 20), controls without detectable specific IgE to common inhalant allergens; group II (n = 22), children sensitized only to non-mite allergens; group III (n = 85), children sensitized to Der p 1. Clinical history of asthma, eczema, and hay fever was ascertained using standardized questionnaires. In total, 43 different HLA class II alleles (DPB, n = 19; DQB, n = 14; and DRB, n = 10) were determined by sequence-specific oligonucleotide typing with PCR-amplified DNA. We were not able to demonstrate significant differences in gene frequencies of any HLA class II allele between the group of mite-sensitized children and one of the other two groups. However, the presence of certain DRB- and DPB-haplotypes (DRB *0100/*0300/*1100 and DPB *0201/*0401) was significantly associated (p < or = 0.01) with a history of asthma, hay fever, and atopy (defined as a history of asthma and/or hay fever and/or eczema). Other haplotypes, including DQB *0303/*0503, DRB *0200/ *0700, and DPB 0402 were negatively associated with a history of eczema, hay fever, and atopy (p < or = 0.01). Thus, our findings do not suggest a relevance of HLA-class II molecules to mite allergy; however, some HLA class II haplotypes appear to be predictive of the incidence of atopic disorders.
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PMID:Mite allergy, clinical atopy, and restriction by HLA class II immune response genes. 879 81

Der f 1, the group I allergen in Dermatophagoides farinae extracts, is a major source of inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f 1 molecule, we found that polyclonal Der f 1-specific short-term T cell lines prepared from peripheral blood of 6 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond to 16 different peptides. Eight of 16 peptides stimulated T cells of more than 2 donors, regardless of the HLA types. Proliferative responses of four T cell lines were markedly inhibited by mAb HU4 (anti-HLA-DRB1+B5), one was inhibited partially by HU11 (anti-HLA-DQ4+5+6), and one was inhibited fully by a combination of HU4, L243 (anti-HLA-DRB1+B4) and PLM16 (anti-HLA-DRB3) but only partially by each of these mAbs. One of these T cell lines, DT, of which the proliferative response was partially inhibited by HU11, was cloned. Indeed, the T cell clones were restricted by DQ6 molecules on an HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. These results indicate that patients' T cells recognize Der f 1 in association mainly with HLA-DRA/DRB1, but that DQAI/DQB1, DRA/DRB3 and possibly DRA/DRB4 gene products also function as antigen-presenting molecules. Thus, although some peptides have a more potent T cell-stimulatory activity than others, the T cell receptor ligands formed with the Der f 1 molecule are highly heterogeneous.
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PMID:Dermatophagoides farinae-1-derived peptides and HLA molecules recognized by T cells from atopic individuals. 910 92

HLA class II polymorphism is variably associated with sensitization to specific allergens, but few convincing HLA associations with asthma or the general state of atopy have been demonstrated. In this study we investigated HLA class II genotype associations with asthma, atopy and specific IgE (sIgE) production to six allergen extracts and six purified major allergens (Der p 1, Der p 2, Fel d 1, Can f 1, Alt a 1 and Phl p 5) in 176 individuals from 20 asthmatic family pedigrees. In selected individuals, cell surface HLA-DR peripheral B-cell expression was correlated with HLA-DRB1 genotype and atopic status. Results showed that HLA-DRB1*08 was negatively associated with asthma (2% vs 17%; Pc = 0.02; OR = 0.08) and atopy (0% vs 16%; Pc = 0.04; OR = 0.1), while DRB1*15 was positively associated with asthma (36% vs 13%; Pc = 0.02; OR = 3.6). Analysis of DRB1 sequences showed that only 29% of individuals with GAG TAC TCT ACG at codons 9-12 in one or both alleles were atopic, compared with 53% of individuals without this sequence (P = 0.002; OR = 0.36). DPA1*0201 was negatively associated with sIgE to both grass pollen mix and Phl p 5 (0% vs 23%; Pc = 0.02; OR = 0.14). A non-significant trend towards higher HLA-DR B-cell expression was seen in both non-atopic and DRB1*08 individuals. In conclusion, this single centre study has demonstrated a number of HLA class II genotype associations with asthma, atopy and sIgE to grass pollen mix and Phl p 5, including hitherto unreported DRB1*08, DRB1 codon 9-12 and DPA1*0201 associations. No significant associations between HLA-DR expression and DRB1 genotype or atopy were demonstrated, although a trend towards higher expression was seen in non-atopic individuals and individuals of DRB1*08 genotype.
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PMID:HLA class II genotype, HLA-DR B cell surface expression and allergen specific IgE production in atopic and non-atopic members of asthmatic family pedigrees. 1064 64

Considerable evidence suggests that IL-10 may have a role in the manifestation of atopic disease. We sought to test the hypothesis that at the single cell level, allergen-specific T cells have diminished IL-10 production capacity in severely affected atopics compared with asymptomatic atopics. We defined three A*0201-restricted Der p 1 CD8(+) T cell epitopes. Using human leukocyte antigen-A*0201-peptide (HLA-A*0201-peptide) tetrameric complexes and enzyme-linked immunospot assays to analyze peripheral blood mononuclear cells from A*0201-positive severely symptomatic atopics, asymptomatic atopics, and nonatopic controls, we observed a significant association between the frequency of the Der p 1-specific CD8(+) T cells and disease activity. The specific T cells expressed an antigen-experienced cell surface phenotype, and 45.7% were positive for cutaneous lymphocyte-associated antigen. The specific T cells were able to produce IFN-gamma efficiently, but their IL-10 production was significantly reduced in severely affected atopics. In contrast, viral-specific CD8(+) T cells were able to produce equivalent amounts of IL-10 in the severely affected atopics compared with asymptomatic atopics and nonatopics. Through defining the first human atopic allergen HLA class I epitopes, we have provided a possible cellular mechanism to link the previous association of low IL-10 levels and severe atopic disease. These data are consistent with a role for CD8(+) T cells in atopic disease pathogenesis and may provide a basis for future T cell immunotherapy strategies.
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PMID:Allergen-specific CD8(+) T cells and atopic disease. 1241 67

Although clinical and laboratory evidence support roles for both staphylococcal infection and environmental allergens in the pathogenesis of atopic dermatitis, human studies have largely considered these variables independently. We sought to test the hypothesis that staphylococcal superantigen influences the allergen-specific T cell response. We first mapped a Der p 1 epitope and used HLA DRB1*1501 class II tetramer-based cell sorted populations to show that specific CD4(+) T cells were able to recognize the peptide presented by HLA DR-matched keratinocytes. We observed that staphylococcal enterotoxin B (SEB) enhanced the IL-4 Der p 1-specific T cell response. This response was mediated by two synergistic mechanisms: first, SEB-induced IFN-gamma promoted class II and intercellular adhesion molecule-1 expression by presenting keratinocytes; and second, SEB-induced IL-4 directly amplified allergen-specific CD4(+) T cell production of many cytokines. We propose that handling of staphylococcal infection is a critical step in the amplification of the allergen-specific T cell response, linking two common disease associations and with implications for the prevention and treatment of atopic disease.
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PMID:Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells. 1737 19