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Examining the origin of peripheral self-reactive T cells and the contribution of Gadd45beta to T cell selection events in the HYcd4 TCR transgenic mouse model Open Access


Other title
TCR transgenic mouse model
T cell negative selection
PD-1 and Gadd45beta
Type of item
Degree grantor
University of Alberta
Author or creator
Kelly, Stephanie Alicia Wilhelmina
Supervisor and department
Baldwin, Troy (Medical Microbiology and Immunology)
Examining committee member and department
Anderson, Colin (Surgery/Medical Microbiology and Immunology)
Cameron, Lisa (Medicine/Pulmonary Research Group)
Kane, Kevin (Medical Microbiology and Immunology)
Department of Medical Microbiology and Immunology
Date accepted
Graduation date
Master of Science
Degree level
Thymic negative selection is important for preventing self-reactive T cells from entering the circulation. However, some self-reactive T cell clones can escape negative selection and induce autoimmunity. The molecular pathways that regulate negative selection are currently unclear, but PD-1 and Gadd45β have been implicated. Using the HYcd4 mouse model, we found an absence of self-reactive CD8SP thymocytes, but the presence of self-reactive T cells in the periphery in adult mice. Ontogeny studies demonstrated the presence of self-specific DP and CD8+ T cells in the periphery at Day 3 post-birth that expressed the co-inhibitory receptor PD-1. The presence of self-reactive T cells was not dependent on negative selection occurring in a neonatal thymus. By studying Gadd45β deficient mice, no evidence was found to support a role for Gadd45β in negative selection. Collectively, these data shed light on the source of self-reactive peripheral T cells and the molecular mechanism underlying negative selection.
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