Signaling from membrane semaphorin 4D in T lymphocytes

• Membrane Sema4D of T lymphocytes can function as a receptor. • Binding of membrane Sema4D causes Lck/ZAP-70 phosphorylation in T lymphocytes. • Signal from membrane Sema4D in naive T lymphocytes is comparable to that from TCR. • Receptor functions of Sema4D appears to be involved in primary T cell activation. 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.