Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Mansour Haeryfar

Second Advisor

Dr. Terry Delovitch

Third Advisor

Dr. Joaquin Madreñas

Abstract

Invariant natural killer T (/NKT) cells are a unique lymphocyte subpopulation with potent immunomodulatory properties. They can produce copious amounts of pro- and/or anti-inflammatory cytokines, yet the mechanisms governing the type of immune responses they elicit are not fully understood. Conventional T cell activation can be achieved or augmented by glycosylphosphatidylinositol (GPI)-anchored proteins. Whether this is also true for /NKT cells is essentially unexplored. I hypothesized that ligation of GPI-anchored proteins such as Thy-1 and CD55 will enhance /"NKT cell activation leading to robust cytokine production. Using flow cytometry, mouse /NKT cells were found to constitutively express Thy-1. Thy-1 engagement combined with classical TCR stimulation led to /NKT cell activation and cytokine production as measured by ELISA and RT-qPCR. Similarly, human /NKT cells expressed CD55, the cross-linking of which enhanced TCR-mediated activation. Overall, I have demonstrated that GPI-anchored proteins play a significant role in the magnitude of /NKT cell responses.

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