Organ-specific and non-organ-specific lymphocyte receptors for vascular endothelium.

The recirculation of lymphocytes from blood to lymph and back to blood is necessary for the proper functioning of the immune system as it facilitates interactions between antigen-reactive clones of lymphocytes and antigen-presenting cells. The first step in the emigration of a blood-borne lymphocyte into either a secondary lymphoid organ or an inflammatory lesion is its adherence to vascular endothelial cells (EC) lining unique post-capillary venules known as high endothelial venules (HEV). Several groups have recently cloned and sequenced genes which may encode organ-specific lymphocyte receptors for the EC of such HEV. The extracellular portion of the putative murine lymphocyte homing receptor for peripheral lymph node HEV is composed of an N-terminal lectin-like domain, followed by an epidermal growth factor-like domain, and then two identical repeating domains which are homologous to a number of complement-binding proteins. A hydrophobic transmembrane domain and a cytoplasmic tail complete the structure. A very similar gene structure has been reported for a cytokine-inducible EC surface protein which is involved in neutrophil-EC adhesion in vitro. In marked contrast, the gene for a putative human lymphocyte homing receptor appears to belong to a gene family which encodes cell-surface molecules with receptor activity for extracellular matrix (ECM) proteins. Similarly, the cell-surface molecule which appears to be the murine lymphocyte receptor for Peyer's patch HEV is homologous, if not identical, to the human VLA-4 molecule, another receptor with binding activity for an ECM protein. It has also been demonstrated that lymphocyte function-associated antigen 1 (LFA-1) acts in a non-organ-specific manner to mediate lymphocyte-EC adhesion. Finally, other non-organ-specific lymphocyte adhesion molecules for EC may include CD4 and CD8 (which bind to class II and class I MHC antigens, respectively), and CD2 (which binds to LFA-3).