The development and function of self-specific CD8 T cells
department or school: Science, Faculty of
department or school: Microbiology and Immunology, Department of
data provider: DSpace
degree campus: UBCV
creator: Dhanji, Salim
issued: 2010-01-16T17:46:36Z
issued: 2006
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: A distinguishing feature of conventional T cells is that they are tolerant to self-peptides that are presented by self-major histocompatibility complex (MHC) molecules even though these cells are positively selected by low affinity interactions between their TCRs and self-peptide/MHC ligands in the thymus. Over the last few years several subsets of unconventional T cells have begun to emerge which often rely on strong interactions between their TCRs and self-antigens for both their development and function. Furthermore, these unconventional T cells often express receptors that are not commonly associated with T cells but rather are associated with cells of the innate immune system. The work in this thesis is focused on the discovery and characterization of a novel subset of CD8 T cells which demonstrate a high affinity for self-antigens and are thus self-specific. These self-specific CD8 T cells can be found in normal mice as well as in self-antigen expressing TCR transgenic mice. Self-specific CD8 T cells are selected by high-affinity interactions either in the thymus or extrathymically and possess a memory-phenotype. As a consequence of this memory-phenotype, which is associated with high expression of CD122 (IL-2Rβ), these cells can proliferate in an antigen-independent manner in response to stimulation with interleukin-2 or -15. Upon activation, the cells express several natural killer cell receptors including NKG2D, CD94, 2B4, and CD16. These NK receptors can act independently or in concert with the self-specific TCR leading to target cell killing and cytokine production. Self-specific CD8 T cells require self-antigen interactions not only for their development but also for the maintenance of their memory-phenotype and cytokine responsiveness. These cells become activated in response to infection or inflammation and this activation results in the innate production of cytokines such as IFNγ which are protective during infection. Thus, self-specific CD8 T cells r…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/18272
note: THE D E V E L O P M E N T AND FUNCTION OF SELF-SPECIF IC CD8 T C E L L S by Salim Dhanji B . S c , University of British Columbia, 2001 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE D E G R E E OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies Microbiology THE UNIVERSITY OF BRITISH COLUMBIA July 2006 © Salim Dhanji, 2006 II Abstract A distinguishing feature of conventional T cells is that they are tolerant to self-peptides that are presented by self-major histocompatibility complex (MHC) molecules even though these cells are positively selected by low affinity interactions between their T C R s and self-peptide/MHC ligands in the thymus. Over the last few years several subsets of unconventional T cells have begun to emerge which often rely on strong interactions between their T C R s and self-antigens for both their development and function. Furthermore, these unconventional T cells often express receptors that are not commonly associated with T cells but rather are associated with cells of the innate immune system. The work in this thesis is focused on the discovery and characterization of a novel subset of CD8 T cells which demonstrate a high affinity for self-antigens and are thus self-specific. These self-specific CD8 T cells can be found in normal mice as well as in self-antigen expressing T C R transgenic mice. Self-specific CD8 T cells are selected by high-affinity interactions either in the thymus or extrathymically and possess a memory-phenotype. As a consequence of this memory-phenotype, which is associated with high expression of CD122 (IL-2RP), these cells can proliferate in an antigen-independent manner in response to stimulation with interleukin-2 or -15. Upon activation, the cells express several natural killer cell receptors including NKG2D, CD94, 2B4, and CD16. These NK receptors can act independently or in concert with the self-specific T C R leading to target cell killing and cytokine production. Self-specific CD8 …
has type: Thesis/Dissertation
date issued: 2006-11
is shown at: 10.14288/1.0092905
language: eng
degree discipline: Microbiology and Immunology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/18272