%0 Thesis
%A van Dijk, Hannah
%T Single-cell based assessment of the human T cell response against Plasmodium falciparum circumsporozoite protein
%I Universität Heidelberg
%V Dissertation
%M DKFZ-2024-02662
%D 2024
%Z Dissertation, Universität Heidelberg, 2024
%X The human malaria parasite Plasmodium falciparum (Pf) is a unicellular organism that infects hepatocytes before reaching the symptom-causing blood stage. The development of a T cell vaccine that could target the liver stage and prevent disease onset remains a challenge. Circumsporozoite protein (CSP) is expressed in infected hepatocytes and elicits a protective antibody response, making it a promising vaccine target. While several CSP T cell epitopes have been described, information of T cell receptor (TCR) gene sequence features, HLA restriction and effects of vaccination on the TCR repertoire are largely unknown. Here, I assessed the human CD8 and CD4 T cell response to CSP after repeated vaccination with recombinant full-length protein compared to pre-vaccination time points at single-cell level. By TR gene repertoire sequencing and the generation of large numbers of transgenic T cell lines expressing representative TCRs, I tracked the clonal dynamics of the CD4 and CD8 T cells over time and assessed the target epitopes of CSP-reactive TCRs and their HLA-linkage. I demonstrate that the activated CD8 T cell pool shows limited clonal diversity at baseline. Prior to vaccination, individual clones comprised up to 10
%K 500 Natural sciences and mathematics (Other)
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%R 10.11588/HEIDOK.00035462
%U https://inrepo02.dkfz.de/record/295845