Fig. 4. Involvement of Sema4A in T cell activation through Tim-2. Sema4A, preferentially expressed on DCs and B cells, is a class IV transmembrane-type semaphorin family member. Tim-2, a member of the Tim protein family, possesses an Ig-like domain, a mucin domain, a transmembrane region, and a cytoplasmic region containing a consensus tyrosine phosphorylation site. The mucin domain has multiple putative sites for O-linked glycosylation, while the Ig domain has several sites for putative N-linked glycosylation. Following T cell activation through TCR ligation, Tim-2 expression on T cells interacts with Sema4A, resulting in enhanced T cell activation via tyrosine phosphorylation of Tim-2, acting through an unknown signaling pathway.