Frequency and phenotype of Fel d 1-specific T cells after peptide therapy

肽治疗后 Fel d 1 特异性 T 细胞的频率和表型

• 批准号: 9037572
• 负责人: Mark Larche
• 金额: $ 66.59万
• 依托单位: MCMASTER UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9037572
• 关键词: Address; Affect; Affinity; Allergens; Allergic Disease; Allergic rhinitis; Archives; Asthma; B-Lymphocytes; Binding; Blood; Cat allergy; Cell physiology; Cells; Clinical; Clinical Trials; Development; Disease; Extrinsic asthma; Felis catus; Freezing; Frequencies; Future; Genes; HLA-DR4 Antigen; Human; Immunotherapy; In Vitro; Instruction; Interleukin-10; Investigational Therapies; MHC Class II Genes; Magnetism; Memory; Molecular Profiling; Mus; Peptide Vaccines; Peptide/MHC Complex; Peptides; Peripheral Blood Mononuclear Cell; Phase II Clinical Trials; Phenotype; Property; Public Health; Reagent; Regulatory T-Lymphocyte; Research Institute; Research Proposals; Severities; T-Lymphocyte; T-Lymphocyte Epitopes; Universities; Vaccines; chemokine receptor; clinical efficacy; cytokine; human subject; novel; prospective; receptor expression; treatment duration; vaccine development

PROJECT SUMMARY (See instructions): The broad, long term objective of this research proposal is to understand how peptide immunotherapy, using validated T cell epitopes of a major allergen (Fel d 1), modulates the frequency and functional phenotype of Fel d 1-specific T cells, using unique MHC Class II tetramer reagents. We hypothesize that peptide immunotherapy results in modulation of the frequency and functional phenotype of allergen-specific T cells following peptide immunotherapy. Specific Aim 1 will determine the effects of peptide immunotherapy (PIT) on Fel d 1-specific (tetramer+) T cells in subjects with cat allergic asthma of increasing severity. An archive of frozen peripheral blood mononuclear cells (PBMC) collected from a Phase II clinical trial of peptide immunotherapy in subjects with cat allergic asthma (groups stratified for severity) will be used to determine the frequency and functional phenotype of allergen-specific (MHC class II tetramer+) T cells. Specific Aim 2 will employ a prospective clinical trial of peptide immunotherapy in cat allergic rhinitis. Large volumes (200ml) of blood will be drawn at baseline, shortly after the end of treatment (week 18-22) and one year after the initiation of the study. Tetramer+ T cells will be enriched using sequential magnetic purification to determine whether peptide immunotherapy changes frequency, memory phenotype, chemokine receptor expression and markers of regulatory T cell function among allergen-specific tetramer+ T cells. Specific Aim 3 will address how the affinity of vaccine peptides for the MHC affects the clinical efficacy of the peptide (its ability to induce immunological tolerance). This study cannot be performed in human subject due to the complexity of MHC molecules expressed and because each peptide binds to multiple MHC molecules. Therefore the study will be conducted in mice that express the human MHC gene, HLA-DR4. The 7 peptides comprising the peptide vaccine employed in Aims 1 & 2 have differing affinity for HLA-DR4. Each peptide will be evaluated to determine how efficacy relates to affinity.

项目概述（见说明）：