TY  - THES
AU  - van Dijk, Hannah
TI  - Single-cell based assessment of the human T cell response against Plasmodium falciparum circumsporozoite protein
PB  - Universität Heidelberg
VL  - Dissertation
M1  - DKFZ-2024-02662
PY  - 2024
N1  - Dissertation, Universität Heidelberg, 2024
AB  - 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
KW  - 500 Natural sciences and mathematics (Other)
LB  - PUB:(DE-HGF)11
DO  - DOI:10.11588/HEIDOK.00035462
UR  - https://inrepo02.dkfz.de/record/295845
ER  -