抗原特异性 Tregs 的 2D 亲和力和频率-猫眼课题宝

抗原特异性 Tregs 的 2D 亲和力和频率

批准号：

9171945

负责人：

Brian D Evavold

金额：

$38.79万

依托单位：

EMORY UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2014

资助国家：

美国

项目状态：

已结题

起止时间：

2014-12-01 至 2017-11-30

来源：

https://reporter.nih.gov/project-details/9171945

关键词：

Address Affinity Antigens Autoantigens Autoimmune Diseases Autoimmune Responses Automobile Driving Binding Biological Biological Assay CD28 gene CD3 Antigens Cell membrane Cells Chronic Clinical Treatment Clinical Trials Data Demyelinating Diseases Demyelinations Development Disease Outcome Doctor of Philosophy Eragrostis Experimental Autoimmune Encephalomyelitis Experimental Designs FOXP3 gene Frequencies Generations Goals Health Human Immune response Inflammation Investigation Kinetics Lead Ligand Binding Location Lymph MHC Class II Genes Measures Mediating Modeling Multiple Sclerosis Mus Myelin Peptide/MHC Complex Peripheral Phenotype Plant Roots Play Positioning Attribute Prevention Principal Investigator Production Property Proteins Protocols documentation PubMed Publishing Regulation Regulatory T-Lymphocyte Relapse Reporting Role Sensitivity and Specificity Site Source Specificity Stable Populations Stimulus System T cell response T-Lymphocyte Technology Testing Therapeutic Therapeutic Uses Thymus Gland Time Tissues Work adaptive immune response base in vivo novel oligodendrocyte-myelin glycoprotein preclinical trial public health relevance receptor response stem text searching thymocyte transcription factor two-dimensional

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DESCRIPTION (provided by applicant): Regulatory T cells (Tregs) are critical for proper control of the immune response and play a clear role in regulation of autoimmune disease. Further highlighting their importance, Tregs provide an antigen specific therapy that is currently being evaluated in preclinical and clinical trials. Although they are of unquestioned value, it is difficult to assess Treg specificity for antigen. In fact, many experimental protocols make use of non-specific TCR stimuli such as anti-CD3/anti-CD28 for their activation, and typical assessments of specificity such as peptide: MHC Class II tetramers and functional readouts are not especially effective when applied to Tregs. As TCR specificity and affinity are crucial to any T cell functional response, we need to understand what affinity range works best for optimal Treg use as well as for their differentiation. Our lab is in a unique position to examine questions on TCR specificity and affinity because we have developed a novel assay system based on two dimensional (2D) micropipette technology that provides the most sensitive means currently available to assess these parameters. The prevalent view of thymic derived Tregs (tTreg) in terms of affinity is that their repertoires are comprised of the highest affinity TCRs that escaped negative selection; however, our preliminary data has identified a range of affinities of tTregs specific for myelin oligodendrocyte glycoprotein (MOG). Instead of driving thymocyte negative selection, MOG supports development of thymic derived MOG specific Tregs. We propose that these Tregs will be of therapeutic use and based on our preliminary studies, propose the following two aims to track Treg specificity, location, kinetics, stability, and potency during chronic and relapsing/remitting demyelinating disease. Aim 1: To define MOG-specific Treg affinity and frequency during demyelinating disease- Aim 2: To determine Treg specificity and lineage stability for MOG-

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