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.

概括 TCR信号强度对效应子检查点对保护性CD4 T细胞免疫的影响病毒。我们最近的研究表明，CD4内存的发展需要CD4效应子再次识别抗原从流感病毒到分化为记忆。许多针对安全性优化的非活疫苗，诱导强烈的抗原表现仅几天，并且无法诱导稳健的CD4 T细胞记忆或长寿命B 细胞反应，取决于CD4辅助效应子。初步结果表明需要高剂量的AG。我们建议确定CD4信号强度（剂量和对TCR）对数量的影响 CD4存储器的质量以及专门用于帮助B细胞的CD4效应子。我们将确定是否获得的CD4存储器具有保护性，并且在对疫苗的反应中是否提供高信号强度可以提高其诱导CD4内存和辅助效应子的能力。如果确实确实需要高剂量和亲和力保护性反应的效应阶段，需要更改疫苗策略，以确保信号提供需要。