Department of Biophysical Chemistry, J. Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences, Prague, Czechia.
Laboratory of Leukocyte Signaling, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia.
Front Immunol. 2019 Apr 2;10:618. doi: 10.3389/fimmu.2019.00618. eCollection 2019.
The interaction of T-cell receptors (TCRs) with self- and non-self-peptides in the major histocompatibility complex (MHC) stimulates crucial signaling events, which in turn can activate T lymphocytes. A variety of accessory molecules further modulate T-cell signaling. Of these, the CD4 and CD8 coreceptors make the most critical contributions to T cell sensitivity . Whereas, CD4 function in T cell development is well-characterized, its role in peripheral T cells remains incompletely understood. It was originally suggested that CD4 stabilizes weak interactions between TCRs and peptides in the MHC and delivers Lck kinases to that complex. The results of numerous experiments support the latter role, indicating that the CD4-Lck complex accelerates TCR-triggered signaling and controls the availability of the kinase for TCR in the absence of the ligand. On the other hand, extremely low affinity of CD4 for MHC rules out its ability to stabilize the receptor-ligand complex. In this review, we summarize the current knowledge on CD4 in T cells, with a special emphasis on the spatio-temporal organization of early signaling events and the relevance for CD4 function. We further highlight the capacity of CD4 to interact with the MHC in the absence of TCR. It drives the adhesion of T cells to the cells that express the MHC. This process is facilitated by the CD4 accumulation in the tips of microvilli on the surface of unstimulated T cells. Based on these observations, we suggest an alternative model of CD4 role in T-cell activation.
T 细胞受体 (TCRs) 与主要组织相容性复合物 (MHC) 中的自身和非自身肽相互作用，刺激关键的信号事件，进而激活 T 淋巴细胞。各种辅助分子进一步调节 T 细胞信号。其中，CD4 和 CD8 共受体对 T 细胞的敏感性做出了最重要的贡献。虽然 CD4 在 T 细胞发育中的功能已得到很好的描述，但它在周围 T 细胞中的作用仍不完全清楚。最初认为 CD4 稳定 TCR 与 MHC 中肽之间的弱相互作用，并将 Lck 激酶递送到该复合物。大量实验的结果支持后一种作用，表明 CD4-Lck 复合物加速了 TCR 触发的信号转导，并控制了在没有配体的情况下 TCR 激酶的可用性。另一方面，CD4 与 MHC 的极低亲和力排除了其稳定受体-配体复合物的能力。在这篇综述中，我们总结了 CD4 在 T 细胞中的最新知识，特别强调了早期信号事件的时空组织及其与 CD4 功能的相关性。我们还强调了 CD4 在没有 TCR 的情况下与 MHC 相互作用的能力。它驱动 T 细胞与表达 MHC 的细胞黏附。在未受刺激的 T 细胞表面的微绒毛尖端，CD4 的积累促进了这一过程。基于这些观察，我们提出了 CD4 在 T 细胞激活中作用的替代模型。
