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.