Mechanisms of T Cell Peptide Epitope-Dependent Late Asthmatic Reactions

Abstract

Short peptide sequences corresponding to T cell epitopes have been identified in the major cat allergen Fel d 1. In order to directly activate allergen-specific T cells in cat-allergic asthmatic individuals, peptides were administered by intradermal injection. Subsequently, a proportion of subjects experienced a delayed reduction of airway calibre manifested as a decrease in FEV₁. Changes in lung function occurred approximately 3 h after peptide injection, peaked at 6 h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue typing techniques, it was determined that many of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind individual peptides within the preparation and thus to activate T cells in a major histocompatibility complex (MHC)-restricted fashion. The precise mechanisms whereby MHC-restricted activation of allergen-specific T cells gives rise to bronchoconstriction are currently under investigation.

Phenotypic analysis of perennial airborne allergen‐specific CD4+ T cells in atopic and non‐atopic individuals

“…As the dominant allergen, Fel d 1 is an ideal model for the design of novel approaches of specific immunotherapy. Fel d 1 appears to have the potential to provide a safe and more specific treatment option for cat‐allergic patients, whether it is with hypoallergens, with peptides containing T cell epitopes, or with fusion proteins of the allergen with various immunomodulatory molecules [16, 17].…”

Omalizumab treatment downregulates dendritic cell FcεRI expression

“…2 DC expression of FcεRI enhances the presentation of allergen to T cells through an antigen-focusing mechanism, in which FcεRI-bound IgE on APCs preferentially captures allergen. 3 Thus, because of the critical role DCs play in the initiation and T H 2 polarization of allergen-specific immune responses, 4 FcεRI expression by DCs might have important immunologic and clinical consequences. 2 DCs are potent APCs that play a critical role in shaping the adaptive immune response to antigens.…”

Platinum Group Elements Enhance the Allergic Immune Response by Acting on Dendritic Cells

“…Fcε-RI-bound IgE enhances the presentation of allergens to T cells by means of antigen focusing and by allowing the uptake of allergen also at very low concentrations [23]. Moreover, DC are critically involved in the initiation and Th2 polarization of allergen-specific immune responses [32] as they act as the first-line sensors of the antigen they have internalized. We found that the exposure of immature DC to PLGE increases the expression of Fcε-RI on the membrane of DC from atopic donors.…”