Semaphorin 4D (Sema4D) is widely represented in the immune system in both membrane and soluble form, and controls immune processes through the specific receptors - these are generally accepted views. Here, an alternative way of Sema4D-dependent immunoregulation is presented, suggesting its functioning as a receptor. We have shown that activation of membrane Sema4D induces phosphorylation of Lck/ZAP-70 in intact T lymphocytes and enhances it in stimulated T cells. Since Sema4D is constitutively presented on the membrane of T lymphocytes, and classical Sema4D receptors are highly expressed by antigen-presenting cells, the membrane Sema4D can serve as an obligate costimulatory molecule in T lymphocyte priming or T-dependent B cell activation.

Semaphorin 4D（Sema4D）以膜和可溶性形式广泛地存在于免疫系统中，并通过特定的受体控制免疫过程-这些是公认的观点。在这里，提出了Sema4D依赖的免疫调节的另一种方式，表明其作为受体的功能。我们已经表明，膜Sema4D的激活在完整的T淋巴细胞中诱导Lck / ZAP-70磷酸化，并在刺激的T细胞中增强它。由于Sema4D组成性呈递在T淋巴细胞的膜上，并且经典Sema4D受体被抗原呈递细胞高度表达，因此Sema4D膜可在T淋巴细胞引发或T依赖性B细胞活化中充当专职共刺激分子。