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

• 批准号: 10187518
• 负责人: SUSAN L SWAIN
• 金额: $ 20.94万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 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/10187518
• 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 infection; influenza outbreak; influenza virus vaccine; influenzavirus; insight; memory CD4 T lymphocyte; neutralizing antibody; pandemic disease; pathogen; prevent; repaired; response; vaccine delivery

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.

摘要 效应器检查点TCR信号强度对流感保护性CD4T细胞免疫的影响 病毒。 我们最近的研究表明，CD4记忆的发展需要CD4效应器再次识别抗原 从流感病毒中分化为记忆。许多针对安全性进行了优化的非活疫苗会导致 强抗原提呈只有几天，它们不能诱导强大的CD4T细胞记忆或长寿的B细胞 细胞反应，依赖于CD4辅助效应器。初步结果表明，需要高剂量的银。 我们建议确定CD4信号强度，包括TCR的剂量和亲和力，对数量的影响 以及CD4记忆的质量和专用于帮助B细胞的CD4效应器。我们将确定是否 获得的CD4记忆是保护性的，以及在疫苗应答中提供高信号强度是否可以 提高他们诱导CD4记忆和辅助效应器的能力。如果确实需要高剂量和亲和力， 保护性反应的效应器阶段，疫苗策略需要改变以确保信号 提供了所需的。

项目成果

Direct IL-6 Signals Maximize Protective Secondary CD4 T Cell Responses against Influenza.

直接 IL-6 信号可最大限度地提高针对流感的保护性次级 CD4 T 细胞反应。

• DOI: 10.4049/jimmunol.1600033
• 发表时间: 2016
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Strutt,TaraM;McKinstry,KarlKai;Kuang,Yi;Finn,CarolineM;Hwang,JiHae;Dhume,Kunal;Sell,Stewart;Swain,SusanL
• 通讯作者: Swain,SusanL