360 research outputs found

    Shadow Spans; Claire Barclay

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    Editor and author of publication produced to coincide with Claire Barclay's Bloomberg Commission Shadow Spans, a yearlong installation at Whitechapel Gallery. During the exhibition Shadow Spans was punctuated by a series of dance performances made in response to the installation by outstanding British choreographers. The book contains an in-depth interview between curator Kirsty Ogg and the artist, short texts by Henrietta hale, Siobhan Davies and Will Tuckett, alongside an extensive section of full colour installation shots and a DVD documenting the dance performances

    Identification of an immunodominant region of Fel d 1 and characterization of constituent epitopes

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    Background: Characterization of T cell epitopes restricted by common HLA alleles is a powerful tool in the understanding of the immune responses to allergens and for the identification of potential peptides for future peptide immunotherapy (PIT). One important requirement is the identification and use of peptides that will bind to HLA molecules covering a large proportion of the population.Objective: To identify commonly recognized CD4+ T cell epitopes in Fel d 1, restricted through frequently expressed HLA molecules for potential future use in PIT.Methods: HLA matched antigen presenting cells, HLA blocking antibodies, and peptide truncations were used in ELISpot assays to establish HLA-restricted T cell epitopes. Cytokine responses were measured by ex vivo and cultured IFN-?, IL-4, and IL-10 ELISpots.Result: Responses to an immunodominant region of chain 2 were identified in the majority of atopic individuals and epitopes restricted by HLA-DQB1*06 and -DPB1*0401 were characterized in detail. Significantly higher ex vivo IL-4 and lower IFN-? responses were observed to both epitopes in individuals with atopic dermatitis (AD) compared with those without disease. IL-10 responses were significantly lower in those with AD in the individuals with HLA-DPB1*0401.Conclusions: We have identified an immunodominant region of Fel d 1 which is frequently recognized by CD4+ T cells from atopic individuals and contains epitopes that are restricted by very common HLA alleles.<br/

    The Néron-Ogg-Shafarevich Criterion for elliptic curves

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    This text is the required master thesis that the author needs to present in order to obtain his Master’s degree in mathematics. It presents a proof of the Néron-Ogg-Shafarevich Criterion for elliptic curves over complete, discretely valued fields. With that goal, the basics of valuation theory and ramification are also developed, paying special attention to p-adic numbers.Universidad de Sevilla. Máster Universitario en Matemática

    Anti-lymphocyte function associated antigen-1 inhibits T-helper 2 function of human allergen-specific CD4+ T cells

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    Background: Blockade of lymphocyte function associated antigen-1 (LFA-1) is proving successful in the management of psoriasis and other inflammatory skin conditions including atopic dermatitis (AD), but the dependence of allergen-specific CD4+ T-cell function on LFA-1 has not been studied extensively.Objectives: We sought to investigate the potential ability of LFA-1 inhibition to influence keratinocyte presentation of allergen to specific T-helper (Th) 2 cell clones.Methods: Using human leucocyte antigen class II tetrameric complexes, we generated Der p 1-specific DRB1*1501-restricted CD4+ T-cell lines (n = 5) and clones (n = 4) from the peripheral blood of five adults with AD.Results: Using doses of anti-LFA-1 present in vivo, we observed significant inhibition (P &lt; 0·05) of allergen-specific CD4+ T-cell production of interleukin-4 with such inhibition occurring during presentation of allergen by keratinocytes.Conclusions: These data show that at doses present in vivo, LFA-1 blockade inhibits keratinocyte presentation to allergen-specific Th2 cells, suggesting one mechanism through which anti-LFA-1 may be beneficial therapeutically.<br/

    Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells

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    Background: although substantial evidence suggests that T cells are important in the pathogenesis of atopic dermatitis (AD), little is known of the differentiation status of CD4+ T cells specific for common environmental allergens. Objective: to determine the frequency, differentiation phenotype, and function of circulating allergen-specific CD4+ T cells in adult individuals with severe persistent AD and controls. Methods: using tetrameric complexes of an HLA DRB1*0101 restricted epitope from Fel d 1, the major IgE-reactive component of cat dander, we studied ex vivo and cultured T-cell frequency and phenotype in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IFN-gamma, IL-4, and IL-10 enzyme linked immuno-spot analysis. RESULTS: Ex vivo Fel d 1-specific DRB1*0101-restricted CD4+ T cells express high levels of CCR7, CD62L, CD27, and CD28 and proportionately low levels of tissue-specific homing receptors and TH1 and TH2 cytokine production, placing the cells largely within the central memory subgroup. Conclusion: circulating Fel d 1-specific DRB1*0101-restricted CD4+ T cells maintain central memory capacity, consistent with a potential to contribute to persisting clinical atopic disease. Clinical implications: persisting central memory characteristics of allergen-specific CD4+ T cells in individuals with AD may contribute to chronic disease.<br/

    T-cell immunotherapy of allergic disease: the role of CD8+ T cells.

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    PURPOSE OF REVIEW: The scope of this review is to place recent advances in T-cell immunotherapy into an account of our understanding of the potential role of CD8+ T cells in the pathogenesis of allergic disease. RECENT FINDINGS: Studies over the last year suggest that changes in CD8+ T-cell function may represent key events in successful T-cell immunotherapy. The first human human leukocyte antigen class I allergen epitopes have now been described and will provide further insights into the role of allergen-specific CD8+ T cells. SUMMARY: The coupling of recent technical advances in the study of antigen-specific T cells with the knowledge of human allergen class I epitopes will promote rapid progress in the field, with potential consequences for the diagnosis, monitoring and immunotherapeutic treatment of affected individuals

    Detection of antigen-specific cytotoxic T lymphocytes: significance for investigative dermatology.

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    Novel recombinant tetrameric complexes of HLA class I molecules allow the direct visualization of antigen-specific CD8+ T cells using flow cytometry. By facilitating the quantification, isolation and phenotypic analysis of CD8+ T cells, the use of HLA tetramers has extended our understanding of the role of cellular immunity in various disease settings. Recently the technique has also been applied to the study of cutaneous disease and provides insights into mechanisms of dermatopathology

    T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection

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    T cells specific for a single viral epitope, but using different T cell receptors, should have flexibility in their epitope recognition to protect the infected host against the emergence of viral escape mutants. Therefore, polyclonality of the hepatitis B virus (HBV)-specific cytotoxic T lymphocyte response has been hypothesized to be a major determinant in the control of infection. We analyzed the V beta chain composition of the core 18-27-specific GD8 cells in acute and persistently HBV-infected patients using HLA-A2 tetrameric complexes and a panel of V beta antibodies. Different T cell receptors were utilized by core 18-27-specific CD8 cells both in patients with acute and chronic infection. The functional ability of these epitope-specific T cells to respond to potential viral mutations was then tested. The polyclonal HBV-specific CD8 response present in patients with acute hepatitis displayed a limited efficiency to recognize mutations introduced within the epitope. The ability of core 18-27-specific CD8 to tolerate epitope mutations was found only during persistent HBV infection. The data suggest that although a clonally heterogeneous CD8 response can be largely inhibited by the occurrence of single epitope mutations in primary HBV infection, preferential selection of T cells able to counteract the emergence of viral mutations can occur during persistent infection
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