Human T-cell responses to ragweed allergens: Amb V homologues.
Specific IgE and IgG responses to highly purified Ambrosia (ragweed) allergens, Amb a V, Amb t V and Amb p V from the artemisiifolia (short), trifida (giant) and psilostachya (western) species are strongly associated with HLA-DR2 and Dw2 (DR2.2) in allergic Caucasoid individuals. To investigate the molecular basis of these HLA associations, we examined the human T-cell responses to these Amb V homologues using three Amb a V-specific, DR alpha beta I 2.2-restricted T-cell clones from an atopic patient. We first examined the cross-reactivity of Amb a V-specific T-cell clones upon challenge with the Amb a V homologues, Amb t V and Amb p V, in the presence of autologous antigen-presenting cells (APC). Neither Amb t V nor Amb p V was able to stimulate the T-cell clones directly. However, both Amb t V and Amb p V specifically blocked, in a dose-dependent fashion, the ability of APC to present Amb a V to all three T-cell clones. Taken together, these results suggest that Amb t V and Amb p V possess distinct T-cell epitopes, but that all Amb V homologues share similar or identical regions (agretopes) interacting with the DR alpha beta I 2.2 (DR alpha beta I 1501) heterodimer. The agretope was potentially localized to a 14-residue C-terminal Amb a V peptide (with Ala-Cys substitutions), which was able to block presentation of native Amb a V by the APC to the T-cell clones.
Huang
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SK
Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
Marsh
D G
DG
D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*