Dissecting the crosstalk between inhibitory receptor signaling and the T cell receptor in natural killer cells
| dc.contributor | Graduate Program in Molecular Biology and Genetics. | |
| dc.contributor.advisor | Sütlü, Tolga. | |
| dc.contributor.author | Ergün, Ebru Zeynep. | |
| dc.date.accessioned | 2023-10-15T17:02:23Z | |
| dc.date.available | 2023-10-15T17:02:23Z | |
| dc.date.issued | 2022 | |
| dc.description.abstract | Killer-cell immunoglobulin-like receptors (KIRs) are among the most prominent receptors regulating NK cell development and function. Most KIR ligands are the MHC class I molecules found on target cells. KIRs are responsible for NK cell licensing which is required for the NK cell to kill and differentiate self from non-self. Adoptive cell therapy based on T cell transfer relies on T cell receptor (TCR) or chimeric antigen receptor (CAR). However, with the TCR-T cells, the most important challenge is mispairing of transferred TCR chains with the endogenous TCR chains. Recently, TCR modification of NK cells has been applied as a solution to the mispairing of TCR chains in T cells. NK cells, with their similar downstream signaling machinery to T cells, can replace T cells in TCR-T cell therapy. These modifications were performed on NK92 cells that lacks inhibitors. This study tries to elucidate how inhibitory signals interfere with TCR signaling. TCR-NK cells against the melanoma-associated antigen Tyrosinase, have been transduced with KIR2DL1 coding lentiviral particles for stable KIR2DL1 expression. The function of the TCR-NK-KIR2DL1 cells was measured against K562 or melanoma cells A375 and A375Tyr. The degranulation of TCR-NK-KIR2DL1 cells was observed to be slightly higher independent from the antigen. Similarly, real- time cell analysis showed the cytotoxicity induced by KIR2DL1 did not show a significant difference. Cy tokine secretion showed there might be a KIR2DL1-mediated TNF-α decrease against A375Tyr cells, but not the same for IFN-γ secretion. Phospho- protein analysis of TCR-NK-KIR2DL1 showed a decrease in PLCγ1 and Erk1/2 levels against all targets. | |
| dc.format.pages | xvi, 80 leaves | |
| dc.identifier.other | BIO 2022 E75 | |
| dc.identifier.uri | https://digitalarchive.library.bogazici.edu.tr/handle/123456789/19937 | |
| dc.publisher | Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022. | |
| dc.subject.lcsh | T cells -- Receptor. | |
| dc.subject.lcsh | Immunoglobulins. | |
| dc.title | Dissecting the crosstalk between inhibitory receptor signaling and the T cell receptor in natural killer cells |
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