Subunit Infection & immune regulation – Dr. Angelique Hölzemer

The group studies how nonclassical HLA-I molecules affect antiviral responses and HIV-induced inflammation of the central nervous system in 3D-organoid models and with functional analysis of human immune cell subsets.

By presenting viral protein on the surface of infected cells, classical Human leukocyte antigen class I (HLA-I) molecules activate antiviral responses while maintaining self-tolerance under healthy conditions. Nonclassical HLA-I molecules (HLA-F, HLA-E and HLA-G) shape innate and adaptive immune responses in mechanisms distinct from antigen presentation. The group studies how nonclassical HLA-I molecules are regulated under inflammatory conditions and during viral infection, focusing on the Human Immunodeficiency Virus (HIV). We further investigate how nonclassical HLA-I molecules modulate the function of cytotoxic effector cells such as natural killer cells and CD8⁺ T cells in the peripheral blood and in the highly tolerogenic environment of the liver. Here, tolerance mechanisms can result in ineffective antiviral immune responses, but are essential to prevent autoimmune liver disease. For theis studies, the group focuses on human culture systems such as 3D-hepatic organoid models and functional investigation of human immune cell subsets from patient cohorts and healthy individuals.

Ongoing immune inflammation predisposes HIV-1 infected individuals to the development of HIV-1 associated neurodegeneration. As a second line of research, the group investigates inflammation in the central nervous system driven by HIV-1 infection. HIV-1 infection of macrophages and microglia is studied in human induced pluripotent stem cell-derived cerebral organoids. This neuro-immune 3D-culture model consists of neurons and glial cells and allows to investigate the direct link between activated microglia and neuronal damage.

Ongoing Research Projects:

• Natural killer cell regulation of T cells in HIV-1 infection
• Microglia in HIV-1 associated neurodegeneration
• The role of HLA-F in liver inflammation and virus infection
• Nonclassical HLA-I (HLA-F and HLA-E)-dependent immune responses in HIV-1

Current Group Members:

• Leonore Mensching Ph.D. (Postdoctoral researcher)
• M. Sc. Sébastien Brias (PhD student)
• M. Sc. Timo Trenkner (PhD student)
• Malte Lingstaedt (cand. med.)
• Maya Beiersdorfer (cand. med.)
• Sandra Köllmann (Lab manager)
• Friederike Reinsberg (Clinician Scientist)

^{Picture (from left to right):}

^{Cerebral organoid culture (©Leonore Mensching), tSNE plot of NK cells (©Leonore Mensching), flow cytometry of HIV-1 infected CD4+ T cells (©Angelique Hölzemer)}