Mechanisms of T cell peptide epitope-dependent late asthmatic reactions.
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 FEV(1). 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.
Larché
M
M
Allergy and Clinical Immunology, Imperial College School of Medicine, London, UK. m.larche@ic.ac.uk
Haselden
B M
BM
Oldfield
W L
WL
Shirley
K
K
North
J
J
Meng
Q
Q
Robinson
D S
DS
Ying
S
S
Kay
A B
AB
D000818:Animals; D001249:Asthma / Q000276:immunology*; D002415:Cats; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D005541:Forced Expiratory Volume; D006023:Glycoproteins / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006023:Glycoproteins; D006684:HLA-DR Antigens; D010455:Peptides; C059296:Fel d 1 protein, Felis domesticus