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ThesisJan 2019

Entwicklung von Methoden zur gezielten Rezeptor-spezifischen Einschleusung von Antigenen in antigen-präsentierende Zellen für die Funktionsdiagnostik humaner T-Lymphozyten in-vitro

Habib, FM
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Abstract
Professional antigen presenting cells (APC) play an important role in cellular immune responses. In this case, APCs as B lymphocytes, dendritic cells and macrophages acquire antigens by cell surface expression. Antigen presentation is performed using surface proteins of the MHC molecules. This presents the internalized antigen to naive T cells. Antigen processing is differentiated by MHC-I to CD8 + - cytotoxic T cells and by MHC-II to CD4 + T helper cells. Compared to B cells, the dendritic cells have the ability to initiate a cytotoxic immune response. Antigen uptake and presentation on the MHC-I complex of CD8 + lymphocytes are referred to as cross-presentation. After activation of the B cell by the binding of CD4 + T cells, cell proliferation is induced to memory and plasma cells. This leads to antibody production against a particular antigen of the plasma cells. Antibodies are responsible for the humoral immune response. They bind to the key-lock principle and with a high affinity for antigens. As tools, recombinant antibodies, e.g. from alpaca derived single-body domains (nanobody), as promising systems. Because of the antigen presenting site and the low molecular weight, nanobodies have significant advantages in biotechnology and medical applications than conventional monoclonal antibodies. In the present study, the antigens influenza and cytomegalovirus (CMV) are used as virus models. According to estimates by the WHO (World Health Organization), influenza viruses cause up to 15% of the world's population to become infected with dangerous symptoms every year. Cytomegalovirus, also known as Human Herpesvirus 5 (HHV 5), is one of the world's largest viral infections, with approximately 70% of infected people in the world's population. In contrast to the influenza virus, cytomegalovirus causes lifelong latency in humans. With the help of genetic engineering methods, cloning allows the assembly of different DNA sequences in one vector. Subsequent stimulation of the recombinant fusion proteins to APCs determines the detection of T cell activity in the flow cytometer.
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