The tyrosine phosphatase CD45 is a major gatekeeper for restraining T cell activation. Its exclusion from the immunological synapse (IS) is crucial for TCR signal transduction. Here, we used expansion super-resolution microscopy to reveal that CD45 is pre-excluded from the tips of microvilli on primary T cells prior to antigen encounter. This pre-exclusion was diminished by depleting cholesterol or by engineering the transmembrane domain of CD45 to increase its membrane integration length, but was independent of the CD45 extracellular domain. We further show that brief microvilli-mediated contacts can induce Ca2+ influx in mouse antigen-specific T cells engaged by antigen-pulsed APCs. We propose that the absence of CD45 phosphatase activity at the tips of microvilli enables or facilitates TCR triggering from brief T cell-APC contacts before formation of a stable IS, and that these microvilli-mediated contacts represent the earliest step in the initiation of a T cell adaptive immune response.

中文翻译：

---

微绒毛尖端的CD45预排除建立了早期TCR触发的无磷酸酶区域

酪氨酸磷酸酶CD45是抑制T细胞活化的主要守门员。将其从免疫突触（IS）中排除对于TCR信号转导至关重要。在这里，我们使用扩展超分辨率显微镜来揭示CD45在抗原遇到之前已从初级T细胞上的微绒毛尖端中排除。通过排除胆固醇或通过工程化CD45的跨膜结构域以增加其膜整合长度，可以减少这种预先排除，但与CD45细胞外结构域无关。我们进一步表明，短暂的微绒毛介导的接触可以诱导抗原脉冲APC参与的小鼠抗原特异性T细胞中的Ca2 +流入。