Although semaphorins were identified originally as guidance cues for developing neuronal axons, accumulating evidence indicates that several semaphorins are expressed also in the immune system. SEMA4D (CD100), which is expressed constitutively by T cells, enhances the activation of B cells and dendritic cells (DCs) through its cell-surface receptor, CD72. SEMA4A, which is expressed by DCs, is involved in the activation of T cells through interactions with TIM2. So, these semaphorins seem to function in the reciprocal stimulation of T cells and antigen-presenting cells (APCs). Emerging evidence indicates that additional semaphorins and related molecules are involved in T-cell-APC interactions also.