How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by this highly reactive beta chain, we generated TCRβ1 transgenic mice. Unexpectedly, TCRβ1 transgenic mice failed to develop spontaneous disease and were also resistant to standard EAE induction by MOG immunization. Despite the absence of disease, ~5% of TCRβ1 transgenic CD4+ T cells from unimmunized mice were MOG-specific, and these further expanded in response to MOG immunization. Three independent transfer models, including transfer of in vitro activated TCRβ1 splenocytes, transfer of TCRβ1 bone marrow, and a mock retrogenic system, all resulted in EAE in recipient mice, indicating there is no T cell-intrinsic blockade to pathogenesis. MOG-responsive transgenic T cells also expressed higher levels of PD-1 and Lag3 in comparison to those from WT and 2D2 mice, suggesting that they might be more prone to exhaustion. TCRβ1 transgenic T cells secreted higher levels of inflammatory cytokines IFN-γ and IL-17 relative to WT T cells, however these levels were comparable to those in pathogenic 2D2 MOG-responsive T cells. These results suggest that tolerance mechanisms in TCRβ1 transgenic mice prevent T cell pathogenicity and disease. Further studies are needed to fully resolve the mechanisms responsible for protection.
","abstract_html":"<p>How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by this highly reactive beta chain, we generated TCRβ1 transgenic mice. Unexpectedly, TCRβ1 transgenic mice failed to develop spontaneous disease and were also resistant to standard EAE induction by MOG immunization. Despite the absence of disease, ~5% of TCRβ1 transgenic CD4+ T cells from unimmunized mice were MOG-specific, and these further expanded in response to MOG immunization. Three independent transfer models, including transfer of in vitro activated TCRβ1 splenocytes, transfer of TCRβ1 bone marrow, and a mock retrogenic system, all resulted in EAE in recipient mice, indicating there is no T cell-intrinsic blockade to pathogenesis. MOG-responsive transgenic T cells also expressed higher levels of PD-1 and Lag3 in comparison to those from WT and 2D2 mice, suggesting that they might be more prone to exhaustion. TCRβ1 transgenic T cells secreted higher levels of inflammatory cytokines IFN-γ and IL-17 relative to WT T cells, however these levels were comparable to those in pathogenic 2D2 MOG-responsive T cells. These results suggest that tolerance mechanisms in TCRβ1 transgenic mice prevent T cell pathogenicity and disease. Further studies are needed to fully resolve the mechanisms responsible for protection. </p>","abstract_has_math":false,"creators":["Wu, Tianhua"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Terrence L. Geiger, MD, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-09-01T07:00:00Z","date_published":"2018-09-01T07:00:00Z","updated_at":"2026-07-24T05:00:33Z","subjects":["autoimmune disease","Experimental Autoimmune Encephalomyelitis","Public TCR","TCR repertoire","Biological Phenomena, Cell Phenomena, and Immunity","Medical Immunology","Medical Neurobiology","Medicine and Health Sciences","Neurosciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/480","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Terrence L. Geiger, MD, PhD"]},{"key":"dc:creator","label":"Author","values":["Wu, Tianhua"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-08-22T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["autoimmune disease","Experimental Autoimmune Encephalomyelitis","Public TCR","TCR repertoire","Biological Phenomena, Cell Phenomena, and Immunity","Medical Immunology","Medical Neurobiology","Medicine and Health Sciences","Neurosciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/480"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by this highly reactive beta chain, we generated TCRβ1 transgenic mice. Unexpectedly, TCRβ1 transgenic mice failed to develop spontaneous disease and were also resistant to standard EAE induction by MOG immunization. Despite the absence of disease, ~5% of TCRβ1 transgenic CD4+ T cells from unimmunized mice were MOG-specific, and these further expanded in response to MOG immunization. Three independent transfer models, including transfer of in vitro activated TCRβ1 splenocytes, transfer of TCRβ1 bone marrow, and a mock retrogenic system, all resulted in EAE in recipient mice, indicating there is no T cell-intrinsic blockade to pathogenesis. MOG-responsive transgenic T cells also expressed higher levels of PD-1 and Lag3 in comparison to those from WT and 2D2 mice, suggesting that they might be more prone to exhaustion. TCRβ1 transgenic T cells secreted higher levels of inflammatory cytokines IFN-γ and IL-17 relative to WT T cells, however these levels were comparable to those in pathogenic 2D2 MOG-responsive T cells. These results suggest that tolerance mechanisms in TCRβ1 transgenic mice prevent T cell pathogenicity and disease. Further studies are needed to fully resolve the mechanisms responsible for protection.
"]},{"key":"dc:title","label":"Title","values":["Pathogenicity and Protection Mediated by a Single TCRβ in Experimental Autoimmune Encephalomyelitis"]}]}],"canonical_facts":{"dc:contributor":["Terrence L. Geiger, MD, PhD"],"dc:creator":["Wu, Tianhua"],"dc:date.available":["2019-08-22T07:00:00Z"],"dc:description.abstract":["How the TCR repertoire, together with risk-associated major histocompatibility complex (MHC), imposes susceptibility for autoimmune disease is not fully understood. A small fraction of TCR α or β chains are “public”, and are shared by most individuals.High-throughput sequencing of the mouse TCRβ repertoire during myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmuneencephalomyelitis (EAE) identified a public TCRβ chain, TCRβ1, which was highly shared among individual mice and preferentially deployed during EAE. Retrogenic expression of TCRβ1 resulted in spontaneous early-onset EAE in mice with high penetrance and severity, despite being paired with a diverse endogenous TCRα repertoire. To further study autoimmunity conferred by this highly reactive beta chain, we generated TCRβ1 transgenic mice. Unexpectedly, TCRβ1 transgenic mice failed to develop spontaneous disease and were also resistant to standard EAE induction by MOG immunization. Despite the absence of disease, ~5% of TCRβ1 transgenic CD4+ T cells from unimmunized mice were MOG-specific, and these further expanded in response to MOG immunization. Three independent transfer models, including transfer of in vitro activated TCRβ1 splenocytes, transfer of TCRβ1 bone marrow, and a mock retrogenic system, all resulted in EAE in recipient mice, indicating there is no T cell-intrinsic blockade to pathogenesis. MOG-responsive transgenic T cells also expressed higher levels of PD-1 and Lag3 in comparison to those from WT and 2D2 mice, suggesting that they might be more prone to exhaustion. TCRβ1 transgenic T cells secreted higher levels of inflammatory cytokines IFN-γ and IL-17 relative to WT T cells, however these levels were comparable to those in pathogenic 2D2 MOG-responsive T cells. These results suggest that tolerance mechanisms in TCRβ1 transgenic mice prevent T cell pathogenicity and disease. Further studies are needed to fully resolve the mechanisms responsible for protection.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/480"],"dc:subject":["autoimmune disease","Experimental Autoimmune Encephalomyelitis","Public TCR","TCR repertoire","Biological Phenomena, Cell Phenomena, and Immunity","Medical Immunology","Medical Neurobiology","Medicine and Health Sciences","Neurosciences"],"dc:title":["Pathogenicity and Protection Mediated by a Single TCRβ in Experimental Autoimmune Encephalomyelitis"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T05:00:33Z"}