The selectins (Fig. 9.7) are important for specifically guiding leukocytes to particular tissues, a phenomenon known as leukocyte homing. L-selectin (CD62L) is expressed on leukocytes, whereas P-selectin (CD62P) and E-selectin (CD62E) are expressed on vascular endothelium (see Section 3-18). L-selectin on naive T cells guides their exit from the blood into secondary lymphoid tissues by initiating a light attachment to the wall of the HEV that results in the T cells’ rolling along the endothelial surface (see Fig. 9.6). P-selectin and E-selectin are expressed on the vascular endothelium at sites of infection, and serve to recruit effector cells into the infected tissue. Selectins are cell-surface molecules with a common core structure and are distinguished from each other by the presence of different lectin-like domains in their extracellular portion. The lectin domains bind to particular sugar groups, and each selectin binds to a cell-surface carbohydrate. L-selectin binds to the carbohydrate moiety—sulfated sialyl-LewisX—of mucin-like molecules called vascular addressins, which are expressed on the surface of vascular endothelial cells. Two of these addressins, CD34 and GlyCAM-1 (see Fig. 9.7), are expressed on high endothelial venules in lymph nodes. A third, MAdCAM-1, is expressed on endothelium in mucosae, and guides lymphocyte entry into mucosal lymphoid tissue such as the Peyer’s patches in the gut.
The interaction between L-selectin and the vascular addressins is responsible for the specific homing of naive T cells to lymphoid organs. On its own, however, it does not enable the cell to cross the endothelial barrier into the lymphoid tissue. This requires the concerted action of chemokines and integrins.
9-6 Activation of integrins by chemokines is responsible for the entry of naive T cells into lymph nodes.
Naive T cells rolling on the endothelium of HEVs via selectins require two additional types of cell-adhesion molecules to enter secondary lymphoid organs— integrins, and members of the immunoglobulin superfamily. Integrins bind tightly to their ligands after receiving signals that induce a change in their conformation. Signaling by chemokines activates integrins on leukocytes to bind tightly to the vascular wall in preparation for the migration of the leukocytes into sites of inflammation (see Section 3-18). Similarly, chemokines present at the luminal surface of the HEV activate integrins expressed on naive T cells during migration into lymphoid organs (see Fig. 9.6).
An integrin molecule consists of a large α chain that pairs noncovalently with a smaller β chain. There are several integrin subfamilies, broadly defined by their common β chains. We will be concerned here chiefly with the leukocyte integrins, which have a common β2 chain paired with distinct α chains (Fig. 9.8). All T cells express the integrin αL:β2 (CD11a:CD18), better known as leukocyte functional antigen-1 (LFA-1). It enables migration of both naive and effector T cells out of the blood. This integrin is also present on macrophages and neutrophils, and is involved in their recruitment to sites of infection (see Section 3-18).
LFA-1 is also important in the adhesion of both naive and effector T cells to their target cells. Nevertheless, T-cell responses can be normal in individuals genetically lacking the β2 integrin chain and hence all β2 integrins,