Year: 2005
Type: dissertation
Abstract: The study focused on the induction of a T helper cell response against the tumor-associated antigen HER2/neu being commonly overexpressed in breast and ovarian tumors. For this purpose, the extracellular domain of the receptor tyrosine kinase was produced in CHO cells and purified in a two-step FPLC column procedure. The protein antigen was loaded on monocyte-derived dendritic cells to generate highly potent antigen presenting cells for the stimulation of autologous naive CD4+ T lymphocytes in an in vitro priming system. IFN-γ secreting cells were detected as soon as 2 weeks after initiation of DC-T cell microcultures. Unequivocal HER2/neu specificity, however, could only be demonstrated in one T cell line. Due to its CD4/CD8 double positive phenotype, there was strong evidence for clonal selection of a potentially autoreactive T cell, that escaped negative thymic selection. After isolation of the descendant T cell clone F2.5 the potential of these HER2/neu-reactive cells to differentiate to either CD4 or CD8 single positive T cells was demonstrated and found to be dependent on stimulation and growth conditions.
Author: Jochen Metzger
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2746995027