{"id":{"repo_id":"edinburgh","oai_identifier":"oai:era.ed.ac.uk:1842/5911"},"canonical_url":"https://search.dev.ndltd.org/etd/edinburgh/oai:era.ed.ac.uk:1842/5911","repository":{"repo_id":"edinburgh","name":"University of Edinburgh","base_url":"https://era.ed.ac.uk/server/oai/request"},"display":{"title":"Peptide immunotherapy in models of allergic airways disease","abstract":"Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease.","abstract_html":"Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease.","abstract_has_math":false,"creators":["MacKenzie, Karen Joan"],"institution":"The University of Edinburgh","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Schwarze, Jürgen","Anderton, Stephen"],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-11-25","date_published":"2011-11-25","updated_at":"2026-07-24T02:14:22Z","subjects":["peptide","immunotherapy","allergic airways","allergic airways disease","asthma"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1842/5911","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Schwarze, Jürgen","Anderton, Stephen"]},{"key":"dc:creator","label":"Author","values":["MacKenzie, Karen Joan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2012-04-27T13:41:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2012-04-27T13:41:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2011-11-25"]},{"key":"dc:publisher","label":"Institution","values":["The University of Edinburgh"]},{"key":"dc:type","label":"Dc Type","values":["Thesis or Dissertation"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["peptide","immunotherapy","allergic airways","allergic airways disease","asthma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1842/5911"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease."]},{"key":"dc:title","label":"Title","values":["Peptide immunotherapy in models of allergic airways disease"]}]}],"canonical_facts":{"dc:contributor.advisor":["Schwarze, Jürgen","Anderton, Stephen"],"dc:creator":["MacKenzie, Karen Joan"],"dc:date.accessioned":["2012-04-27T13:41:38Z"],"dc:date.available":["2012-04-27T13:41:38Z"],"dc:date.issued":["2011-11-25"],"dc:description.abstract":["Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease."],"dc:identifier.uri":["http://hdl.handle.net/1842/5911"],"dc:language.iso":["en"],"dc:publisher":["The University of Edinburgh"],"dc:subject":["peptide","immunotherapy","allergic airways","allergic airways disease","asthma"],"dc:title":["Peptide immunotherapy in models of allergic airways disease"],"dc:type":["Thesis or Dissertation"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD Doctor of Philosophy"]},"updated_at":"2026-07-24T02:14:22Z"}