{"id":{"repo_id":"kings","oai_identifier":"oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"},"canonical_url":"https://search.dev.ndltd.org/etd/kings/oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637","repository":{"repo_id":"kings","name":"King's College London","base_url":"https://kclpure.kcl.ac.uk/ws/oai"},"display":{"title":"Identification and characterisation of HLA-DRB1*0101 restricted CD4+ T cell epitopes in the major grass pollen allergens Phl p 1 and Phl p 5","abstract":"Over 10 million people in the UK suffer from allergic rhinitis. The majority have symptoms caused by grass pollen exposure. Phl p 1 and Phl p 5 are the major grass pollen allergens in Timothy grass (Phleum pratense). Specific grass pollen immunotherapy using whole extract is an effective disease-modifying treatment, but it is associated with severe, life-threatening systemic IgE-mediated side-effects. One strategy to improve safety and clinical efficacy is to develop peptide immunotherapy for grass pollen allergy.<br/>The aim of this thesis was to identify HLA-DR1-restricted CD4+ T cell epitopes of Phl p 1 and Phl p 5 by complementary approaches of epitope mapping: in silico prediction, tetramer guided epitope mapping and human HLA-DR1 transgenics. I investigated recognition of HLA-DR1-restricted CD4+ T cell epitopes in allergic and non-allergic individuals and characterised epitope-specific CD4+ T cells, according to cell surface markers and cytokine production.<br/>HLA-DR1 transgenics were primed with either Phl p 1 and Phl p 5b protein and the T cell lines generated were screened using a panel of overlapping peptides in 3H-thymidine incorporation assays. HLA-DR1-tetramers loaded with Phl p 1 or Phl p 5b peptides were used in tetramer guided epitope mapping studies using PBMC from HLA-DR1+, grass-allergic, seasonal allergic rhinitis patients. Tetramer-positive populations were detectable in PBMC of &gt;75% of patients studied. Epitope-specific CD4+ T cells were detectable immediately ex vivo in allergic and non-allergic individuals. Data suggest that epitope-specific CD4+ T cells from allergic individuals exhibit an effector memory, Th2-like phenotype.","abstract_html":"Over 10 million people in the UK suffer from allergic rhinitis. The majority have symptoms caused by grass pollen exposure. Phl p 1 and Phl p 5 are the major grass pollen allergens in Timothy grass (Phleum pratense). Specific grass pollen immunotherapy using whole extract is an effective disease-modifying treatment, but it is associated with severe, life-threatening systemic IgE-mediated side-effects. One strategy to improve safety and clinical efficacy is to develop peptide immunotherapy for grass pollen allergy.&lt;br/&gt;The aim of this thesis was to identify HLA-DR1-restricted CD4+ T cell epitopes of Phl p 1 and Phl p 5 by complementary approaches of epitope mapping: in silico prediction, tetramer guided epitope mapping and human HLA-DR1 transgenics. I investigated recognition of HLA-DR1-restricted CD4+ T cell epitopes in allergic and non-allergic individuals and characterised epitope-specific CD4+ T cells, according to cell surface markers and cytokine production.&lt;br/&gt;HLA-DR1 transgenics were primed with either Phl p 1 and Phl p 5b protein and the T cell lines generated were screened using a panel of overlapping peptides in 3H-thymidine incorporation assays. HLA-DR1-tetramers loaded with Phl p 1 or Phl p 5b peptides were used in tetramer guided epitope mapping studies using PBMC from HLA-DR1+, grass-allergic, seasonal allergic rhinitis patients. Tetramer-positive populations were detectable in PBMC of &amp;gt;75% of patients studied. Epitope-specific CD4+ T cells were detectable immediately ex vivo in allergic and non-allergic individuals. Data suggest that epitope-specific CD4+ T cells from allergic individuals exhibit an effector memory, Th2-like phenotype.","abstract_has_math":false,"creators":["Till, Stephen"],"institution":"Imperial College London","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-11-14","date_published":"2013-11-14","updated_at":"2026-07-24T02:44:31Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"],"render_values":[{"text":"oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637","href":null,"code":true}]}]},"links":{"outbound_url":"https://kclpure.kcl.ac.uk/portal/en/studentTheses/137ffa04-055a-416e-98b9-4c8cc3dc7637","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Till, Stephen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-11-14"]},{"key":"dc:date.issued","label":"Date","values":["2013-11-14"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Respiratory Medicine & Allergy"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["Imperial College London"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637","https://kclpure.kcl.ac.uk/portal/en/studentTheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Over 10 million people in the UK suffer from allergic rhinitis. The majority have symptoms caused by grass pollen exposure. Phl p 1 and Phl p 5 are the major grass pollen allergens in Timothy grass (Phleum pratense). Specific grass pollen immunotherapy using whole extract is an effective disease-modifying treatment, but it is associated with severe, life-threatening systemic IgE-mediated side-effects. One strategy to improve safety and clinical efficacy is to develop peptide immunotherapy for grass pollen allergy.<br/>The aim of this thesis was to identify HLA-DR1-restricted CD4+ T cell epitopes of Phl p 1 and Phl p 5 by complementary approaches of epitope mapping: in silico prediction, tetramer guided epitope mapping and human HLA-DR1 transgenics. I investigated recognition of HLA-DR1-restricted CD4+ T cell epitopes in allergic and non-allergic individuals and characterised epitope-specific CD4+ T cells, according to cell surface markers and cytokine production.<br/>HLA-DR1 transgenics were primed with either Phl p 1 and Phl p 5b protein and the T cell lines generated were screened using a panel of overlapping peptides in 3H-thymidine incorporation assays. HLA-DR1-tetramers loaded with Phl p 1 or Phl p 5b peptides were used in tetramer guided epitope mapping studies using PBMC from HLA-DR1+, grass-allergic, seasonal allergic rhinitis patients. Tetramer-positive populations were detectable in PBMC of &gt;75% of patients studied. Epitope-specific CD4+ T cells were detectable immediately ex vivo in allergic and non-allergic individuals. Data suggest that epitope-specific CD4+ T cells from allergic individuals exhibit an effector memory, Th2-like phenotype."]},{"key":"dc:title","label":"Title","values":["Identification and characterisation of HLA-DRB1*0101 restricted CD4+ T cell epitopes in the major grass pollen allergens Phl p 1 and Phl p 5"]}]}],"canonical_facts":{"dc:creator":["Till, Stephen"],"dc:date":["2013-11-14"],"dc:date.issued":["2013-11-14"],"dc:description.abstract":["Over 10 million people in the UK suffer from allergic rhinitis. The majority have symptoms caused by grass pollen exposure. Phl p 1 and Phl p 5 are the major grass pollen allergens in Timothy grass (Phleum pratense). Specific grass pollen immunotherapy using whole extract is an effective disease-modifying treatment, but it is associated with severe, life-threatening systemic IgE-mediated side-effects. One strategy to improve safety and clinical efficacy is to develop peptide immunotherapy for grass pollen allergy.<br/>The aim of this thesis was to identify HLA-DR1-restricted CD4+ T cell epitopes of Phl p 1 and Phl p 5 by complementary approaches of epitope mapping: in silico prediction, tetramer guided epitope mapping and human HLA-DR1 transgenics. I investigated recognition of HLA-DR1-restricted CD4+ T cell epitopes in allergic and non-allergic individuals and characterised epitope-specific CD4+ T cells, according to cell surface markers and cytokine production.<br/>HLA-DR1 transgenics were primed with either Phl p 1 and Phl p 5b protein and the T cell lines generated were screened using a panel of overlapping peptides in 3H-thymidine incorporation assays. HLA-DR1-tetramers loaded with Phl p 1 or Phl p 5b peptides were used in tetramer guided epitope mapping studies using PBMC from HLA-DR1+, grass-allergic, seasonal allergic rhinitis patients. Tetramer-positive populations were detectable in PBMC of &gt;75% of patients studied. Epitope-specific CD4+ T cells were detectable immediately ex vivo in allergic and non-allergic individuals. Data suggest that epitope-specific CD4+ T cells from allergic individuals exhibit an effector memory, Th2-like phenotype."],"dc:identifier":["oai:kclpure.kcl.ac.uk:studenttheses/137ffa04-055a-416e-98b9-4c8cc3dc7637","https://kclpure.kcl.ac.uk/portal/en/studentTheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"],"dc:language":["eng"],"dc:publisher.department":["Respiratory Medicine & Allergy"],"dc:publisher.institution":["Imperial College London"],"dc:relation.isreferencedby":["https://kclpure.kcl.ac.uk/portal/en/studentTheses/137ffa04-055a-416e-98b9-4c8cc3dc7637"],"dc:title":["Identification and characterisation of HLA-DRB1*0101 restricted CD4+ T cell epitopes in the major grass pollen allergens Phl p 1 and Phl p 5"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:44:31Z"}