Mechanisms of T cell peptide epitope-dependent late asthmatic reactions

Short peptide sequences corresponding to T cell epitopes have been identifi ed in the major cat allergen Fel d 1. In order to directly activate allerge n-specific T cells in cat-allergic asthmatic individuals, peptides were adm inistered 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 man y of the individuals experiencing isolated LAR expressed particular HLA-DR molecules. These molecules were shown in subsequent experiments to bind ind ividual peptides within the preparation and thus to activate T cells in a m ajor histocompatibility complex (MHC)-restricted fashion, The precise mecha nisms whereby MHC-restricted activation of allergen-specific T cells g ives rise to bronchoconstriction are currently under investigation. Copyright ( C) 2001S.KargerAG,Basel.