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Impact of TcR Signal Strength at the Effector Checkpoint on Protective CD4 T Cell Immunity to Influenza Virus

效应器检查点 TcR 信号强度对保护性 CD4 T 细胞对流感病毒免疫的影响

基本信息

批准号：
10027026
负责人：
SUSAN L SWAIN
金额：
$ 25.13万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-09 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10027026
关键词：
Adjuvant Affinity Antibodies Antibody Formation Antigen Presentation Antigens Antiviral Agents Attenuated Automobile Driving Avidity B-Lymphocytes CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Capsid Proteins Cells Cessation of life Childhood Core Protein Development Disease Disease Outbreaks Dose Elderly Ensure Epitopes Formulation Gene Expression Profile Generations Immunity Individual Infection Influenza Influenza A virus Interleukin-2 Learning Life Longevity Lung Mediating Membrane Glycoproteins Memory Memory B-Lymphocyte Mus Mutate Oils Pathway interactions Peptides Phase Phenotype Physiological Recombinants Role Safety Signal Transduction Site Structure of germinal center of lymph node Symptoms T cell response T memory cell T-Lymphocyte Tissues Transgenic Organisms Vaccination Vaccine Design Vaccines Variant Virus Water aged autocrine base cell injury cytokine cytotoxic density first responder improved in vivo influenza outbreak influenza virus vaccine influenzavirus insight memory CD4 T lymphocyte neutralizing antibody pandemic disease pathogen prevent repaired response vaccine delivery

项目摘要

SUMMARY Impact of TcR Signal Strength at the Effector Checkpoint on Protective CD4 T Cell Immunity to Influenza Virus. Our recent studies show that the development of CD4 memory requires CD4 effectors to again recognize antigen from influenza virus in order to differentiate to memory. Many non-live vaccines, optimized for safety, induce strong antigen presentation only for a few days and they fail to induce robust CD4 T cell memory or long-lived B cell responses, dependent on CD4 helper effectors. Preliminary results indicate high doses of Ag are needed. We propose to determine the impact of CD4 signal strength, both dose and affinity for the TcR, on the quantity and quality of CD4 memory and on CD4 effectors specialized for helping B cells. We will determine whether the CD4 memory obtained is protective and whether providing high signal strength in responses to vaccine can improve their ability to induce CD4 memory and helper effectors. If high dose and affinity are indeed needed at the effector stage for protective responses, vaccine strategies would need to be altered to ensure the signals needed are provided.

总结效应物检查点TcR信号强度对保护性CD4 T细胞抗流感免疫的影响病毒我们最近的研究表明，CD4记忆的形成需要CD4效应子重新识别抗原从流感病毒中分离出来，以分化为记忆。许多针对安全性进行了优化的非活疫苗，强的抗原呈递仅持续几天，并且它们不能诱导强的CD4 T细胞记忆或长寿命的B 细胞反应，依赖于CD4辅助效应。初步结果表明，需要高剂量的Ag。我们建议确定CD4信号强度的影响，包括剂量和对TcR的亲和力，和CD4记忆的质量以及专门帮助B细胞的CD4效应器。我们将决定是否获得的CD4记忆是保护性的，是否在对疫苗的反应中提供高信号强度可以提高其诱导CD4记忆和辅助效应物的能力。如果确实需要高剂量和亲和力，保护性反应的效应阶段，疫苗策略需要改变，以确保信号需要提供。