Projects

Charité Corona Cross

Initial vaccination strategies focused on inducing a high amount of (neutralizing) antibodies which can prevent the virus from entering the host cells or rapidly clear the virus from the body liquids. The limited antibody persistence and the evolution of escape variants shifted the focus to efficiently induce long-living memory T-cell responses. These T-cell responses have a broader epitope coverage and can efficiently protect against severe disease even upon infection with highly mutated variants. However, the characteristics of protection, especially in vulnerable cohorts such as the elderly and immunosuppressed, remain yet to be defined. Within Charité Corona Protect (CCP), we analyze whether homo- or heterologous vaccination strategies (Henze et al., submitted), quality and longevity of immunity induced by infection or vaccination-mediated boosters (Meyer-Arndt et al., in preparation) provide better immunity. Furthermore, we investigate the quality of (cross)-reactive immune responses in young versus old individuals in the light of existing and potential arising variants of concern (Loyal et al., in preparation).

The 3D Thymus (1° MACSima project)

Initial vaccination strategies focused on inducing a high amount of (neutralizing) antibodies which can prevent the virus from entering the host cells or rapidly clear the virus from the body liquids. The limited antibody persistence and the evolution of escape variants shifted the focus to efficiently induce long-living memory T-cell responses. These T-cell responses have a broader epitope coverage and can efficiently protect against severe disease even upon infection with highly mutated variants. However, the characteristics of protection, especially in vulnerable cohorts such as the elderly and immunosuppressed, remain yet to be defined. Within Charité Corona Protect (CCP), we analyze whether homo- or heterologous vaccination strategies (Henze et al., submitted), quality and longevity of immunity induced by infection or vaccination-mediated boosters (Meyer-Arndt et al., in preparation) provide better immunity. Furthermore, we investigate the quality of (cross)-reactive immune responses in young versus old individuals in the light of existing and potential arising variants of concern (Loyal et al., in preparation).

LINE-1 Immunity

Description will follow

Skin – Vasculature – T cells

Over the last decade, immune-checkpoint inhibitors (ICI) immunotherapy has shown promise as a treatment for melanoma skin cancer. Immune-checkpoint therapy offers different strategies to target and block immune-checkpoint receptors, thus enabling anti-tumour immune response. However, ICI treatment has been limited to a 40-60% response rate in patients and is associated with several immune-related adverse events such as colitis, hypophysitis, hepatitis, pneumonitis, hyperthyroidism, hypothyroidism and type 1 diabetes. This calls for the development of a prediction tool that can identify patients with a greater chance of benefiting from this immunotherapy. Human-relevant platforms for drug testing can potentially better predict human response in clinical studies and present an attractive alternative for an animal testing platform in research. In this project, we aim to achieve an immune-competent human skin-on-a-chip testing platform, that can be used as a personalized prediction tool for ICI effect on patients before treatment. This platform will include a skin-on-a-chip model with circulating T cells composed of autologous cells isolated from the patient’s skin biopsies and blood samples. Establishing such a platform can potentially prevent unnecessary ICI immunotherapy in non-responsive melanoma patients and will allow further investigation of T cell activation and function in human skin.

CD8+ helper T cells

Activated CD4+ T cells transiently express CD40L and provide “help” in terms of APC licensing and/or the necessary stimuli for B cell maturation, somatic hypermutation, and class switching. In contrast, CD8+ T cells are characterized as cytotoxic T cells, that can directly kill infected target cells. However, we previously identified a CD40L expressing CD8+ T cell population, which inherits the ability of DC licensing (Frentsch et al., Blood, 2013). In-depth analysis revealed that CD8+ memory T cells have a CD4+ T cell alike diversity and can differentiate into Tc1, Tc2, Tc17, Tc17+1, and Tc22 subsets. Among them, the Tc2, Tc17, and Tc22 cell subsets lack cytotoxic features, but express high levels of CD40L, and resemble helper CD4+ T cells in their gene expression signature (Loyal et al., Nat. Comms., 2020). We could demonstrate that helper CD8+ T cells do not express the CD8 lineage transcription factor Runx3 which is in contrast present in cytotoxic CD4+ T cells and all cytotoxic cells can be distinguished from helper cells irrespective of their cell type by the expression of SLAMF7 (Loyal et al., Nat. Comms., 2020). In our current projects, we are addressing the questions of how these helper CD8+ T cells are induced and what is their role in human health and disease.

KFO 399

Although the prevalence of IgE-mediated food allergies is on the rise in most industrialized countries, it currently has no known cure. Instead, allergic patients are usually instructed to avoid food containing the allergens they are sensitized to. Our research group is part of the food@ Clinical Research Unit (KFO 339), aiming to desensitize allergic donors using a liberated diet approach: the patients are instructed to regularly consume low doses of allergens below their reaction threshold for one year (as opposed to strict avoidance of the allergens), whilst various bio-samples are collected before and after the clinical intervention. In our group, we are focusing on the identification of immune mechanisms involved in food allergy sensitization and desensitization by monitoring the response to allergens of different immune cell subsets (T cells, B cells, antigen-presenting cells, basophils). Our findings contribute to a better understanding of the immune circuits of food allergy and refine laboratory diagnostic assays.

Publications