Semaphorins in interactions between T cells and antigen-presenting cells

Semaphorins were identified originally as repulsive axon-guidance factors during neuronal development. It is becoming increasingly clear that several members of the semaphorin family have roles in the immune system. SEMA4D (CD100), a class IV semaphorin, uses two receptors, plexin-B1 and CD72, the latter of which is a functional lymphocyte receptor. SEMA4D enhances B-cell responses by a unique mechanism — turning off the negative signals of CD72. SEMA4D also has a role in the generation of antigen-specific T cells by enhancing the activation and maturation of professional antigen-presenting cells, such as dendritic cells (DCs). ;Another class IV semaphorin, SEMA4A, which is expressed preferentially by DCs, is involved in T-cell activation. Molecular cloning has shown that the receptor for SEMA4A is TIM2, which is expressed on the surface of activated T cells and belongs to the T-cell, immunoglobulin domain and mucin domain (TIM) protein family. In addition, other semaphorins (such as SEMA3A and SEMA7A) and semaphorin receptors (such as neuropilins) seem to have roles in immune responses.