Christian Möbs

The significance of B‐cell memory in sustaining IgE‐mediated allergies but also ensuring the development of long‐term allergen tolerance has remained enigmatic. However, well‐thought murine and human studies have begun to shed more light on this highly disputed subject. The present mini review highlights important aspects, like the involvement of IgG1 memory B cells, the meaning of low‐ or high‐affinity IgE antibody production, the impact of allergen immunotherapy, or the relevance of local memory established by ectopic lymphoid structures. Based on recent findings, future investigations should lead to deeper knowledge and the development of improved therapies treating allergic individuals.

Background Immune responses to N‐glycan structures from allergens and parasites are often associated with pronounced, high affinity IgE reactivities. Cross‐reactive carbohydrate determinants (CCDs) are constituted by modified N‐glycan core structures and represent the most frequently recognized epitopes in allergic immune responses. Although recently accepted as potentially allergenic epitopes, the biological and clinical relevance as well as structural and functional characteristics of CCD‐specific antibodies remain elusive. Methods In order to gain structural insights into the recognition of CCDs, two specific antibody fragments were isolated from a leporid immune repertoire library and converted into human/leporid IgE and IgG formats. The antibody formats were assessed by ELISA and surface plasmon resonance, structural and functional analyses were performed by X‐ray crystallography, mediator release, and ELIFAB assays. Results The recombinant IgE exhibited highly specific interactions with different types of CCDs on numerous CCD‐carrying glycoproteins. Crystal structures of two CCD‐specific antibodies, one of which in complex with a CCD‐derived disaccharide emphasize that mechanisms of core glycan epitope recognition are as specific as those governing protein epitope recognition. The rIgE triggered immediate cellular responses via FcεRI cross‐linking and mediated facilitated antigen presentation by binding of IgE/antigen complexes to CD23, a process that also could be blocked by IgG of allergic patients. Conclusions Our study provides evidence for the relevance of N‐glycan recognition in T H 2 responses and corroborates that IgE and IgG antibodies to ubiquitous carbohydrate epitopes can be equivalent to those directed against proteinaceous epitopes with implications for diagnostic and immunotherapeutic concepts.