Signaling in Natural Killer Cells: NK Cell Activation by LLT1 Receptor

Simple item page
dc.contributor.advisorJerry Simecka
dc.contributor.committeeMemberRichard Easom
dc.contributor.committeeMemberHarlan Jones
dc.creatorBambard, Nowland D.
dc.date.accessioned2019-08-22T21:13:11Z
dc.date.available2019-08-22T21:13:11Z
dc.date.issued2008-05-01
dc.date.submitted2013-06-06T07:00:09-07:00
dc.description.abstractBambard, Nowland D., Signaling in Natural Killer Cells: NK Cell Activation by LLT1 Receptor. Doctor of Philosophy (Microbiology and Immunology), May 2008, 162 pp., 1 table, 30 illustrations, bibliography, 179 titles. Natural Killer (NK) cells are large granular lymphocytes of the innate immune system that constitute the first line of defense against viral pathogens and cancer. Unlink cells of the adaptive immune response, NK cells do not recognize specific antigens expressed on MHC receptors, rather they recognize tumorgenic and virally infected cells through a complex balance of activating and inhibiting receptors expressed on the surface of human NK cells. LLT1 is expressed on numerous immune cells and subsequent functional analysis indicates that LLT1 plays an activating role on NK cells by way of stimulating interferon-gamma (IFN-G) secretion. LLT1 has also been shown to have a role on non-immune cells, inhibiting the formation and function of osteoclasts. Additionally, the natural ligand of LLT1 has been identified as NKR-P1A (CD161), an NK cell inhibitory receptor known to play an important role in immune regulation. We hypothesize that LLT1 employs multiple signaling pathways to accomplish its activating functions on human NK cells, and may be associated with one of four known transmembrane accessory proteins associated with NK cell activating receptors. We activated LLT1 on NK92 cells with target cells expressing its natural ligand CD161 and analyzing IFN-G production in the presence of pharmacological inhibitors specific for various signaling mechanisms. These results indicate that LLT1 employs Src-PTK, p38 and ERK signaling pathways, but not PKC, P13K or calcineurin. These results were followed up with phosphorylation analysis, which confirmed that the ERK signaling pathway is associated with LLT1 IFN-G production. Finally, by analyzing IFN-G mRNA we found that LLT1 activation is not associated with any detectable change in IFN-G mRNA levels, suggesting that LLT1 stimulates NK IFN-G production by modulating post transcriptional or translational events. Identification of the signaling pathways associated with LLT1 is of great medical significance as this may provide us with novel insights into activating NK cells to counter infection and cancer.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29164
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectAnatomy
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCells
dc.subjectImmunity
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectOther Cell and Developmental Biology
dc.subjectOther Immunology and Infectious Disease
dc.subjectNatural killer cells
dc.subjectsignaling
dc.subjectNK cell activation
dc.subjectLLT1 Receptor
dc.subjectinterferon-gamma secretion
dc.subjectimmune system
dc.subjectimmunity
dc.subjectNK
dc.subjectNKR-P1A
dc.subjectCD161
dc.subjectIFN-G
dc.subjectNK92
dc.subjectcancer
dc.subjectviral pathogens
dc.titleSignaling in Natural Killer Cells: NK Cell Activation by LLT1 Receptor
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
Bambard_SignalingInNaturalKiller.pdf
Size:
69.93 MB
Format:
Adobe Portable Document Format
Download

Collections

School of Biomedical Sciences
Theses and Dissertations