Tracing antigen signatures in the human IgE repertoire

Abstract

Allergen recognition by IgE antibodies is a key event in allergic inflammation. In this study, the IgE IGHV repertoires of individuals with allergy to the major birch pollen allergen, Bet v 1, were analyzed over a four years period of allergen exposure by RT-PCR and sequencing of cDNA. Approximately half of the IgE transcripts represented non-redundant sequences, which belonged to seventeen different IGHV genes. Most variable regions contained somatic mutations but also non-mutated sequences were identified. There was no evidence for relevant increases of somatic mutations over time of allergen exposure. Highly similar IgE variable regions were found after four years of allergen exposure in the same and in genetically non-related individuals. Our results indicate that allergens select and shape a limited number of similar IgE variable regions in the human IgE repertoire.

Fig. 1

Allergen exposure and allergen-specific IgE levels in the four years study period. Birch pollen exposure expressed as pollen counts per m³ of air (y-axis: pollen count) in the years 2002–2005 (x-axis: months are abbreviated). The time points when PBMCs were obtained from allergic subjects (B, D, H) for the characterization of IgE IGHV regions are indicated (×) and the IgE levels specific for the major birch pollen allergen, Bet v 1 are displayed in kUA/L.

Fig. 2

Frequency of the usage of V genes in the IgE repertoires of the allergic subjects over a four years period. Frequencies (x-axes: absolute numbers of non-redundant sequences) of V genes are displayed for allergic subjects (B, D, H) at different dates (top of the figures).