Search

Background Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease. Objectives To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets. Methods We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses. Results Filaggrin null mutations associated with significantly ( P < 0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses. Conclusions These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease. [ABSTRACT FROM AUTHOR]

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-γ, IL-4, and IL-10 ELISpots. Results 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-γ 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. [ABSTRACT FROM AUTHOR]