Human IgE against the major allergen Bet v 1--defining an epitope with limited cross-reactivity between different PR-10 family proteins.
Bottom Line: The interaction between IgE and allergen is a key event at the initiation of an allergic response, and its characteristics have substantial effects on the clinical manifestation.We here display the usefulness of allergen-specific human monoclonal IgE as a tool in studies of the crucial molecular interaction taking place at the initiation of an allergic response.Such studies may aid us in development of better diagnostic tools and guide us in the development of new therapeutic compounds.
Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.Show MeSH
Mentions: Genetic analysis of VH-encoding sequences of the four Bet v 1-specific antibody fragments reveals that they all originate in the IGHV5 germline subgroup (Table2), a subgroup previously shown to be overrepresented in some IgE-encoding transcriptomes of allergic individuals 4–6. They all originate in the relatively common IGHV5-51 H chain V gene 37, but vary in terms of length of the rearrangement encoding the third complementarity determining region of the H chain (CDRH3) (12-19 codons). Clones B10 and B13 originate from the same VH chain rearrangement and share the same CDRH3, considered to be of crucial importance for antibody specificity 38. They also share some but not all of their substitutions (Fig.2a and Figure S1), suggesting that they have diversified from common precursor through a mutational process. Likewise, clones B14 and M0418 have very similar heavy chain sequences (Fig.2b), primarily differing only by the addition of one codon in the CDRH3 of M0418. They are thus also likely to share a common ancestor. The light chain sequences of these scFv are all diverse (Table2, Figure S2), but they all belong to the λ light chain class of variable domains.
Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.