SEMA4A is a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in guidance of axonal migration during neuronal development and in immune responses.Mice treated with Sema4a had enhanced priming of antigen-specific T cells secreting both IL4 and gamma-interferon (IFNG). Treatment of mice with anti-Sema4a early after immunization with myelin oligodendrocyte glycoprotein suppressed the development of experimental autoimmune encephalomyelitis. In these mice, infiltration of mononuclear inflammatory cells was ablated by inhibition of the generation of antigen-specific T cells by anti-Sema4a. Expression cloning determined that the high-affinity receptor for Sema4a is Tim2. Sema4a stimulation of cells expressing Tim2 induced tyrosine phosphorylation of Tim2 but not of Tim3.
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