Search

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]

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 < 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. [ABSTRACT FROM AUTHOR]