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

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。

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.