In spite of the known MHC complex consisting of binding of a TCR to the pro-cessed antigen, which in turn is bound to the class II molecule of APCs, this is not enough for T-cell activation. One must have additional stimuli that are provided by a series of adhesion molecules on the two cell surfaces.
These molecules are composed of a diverse set of cell-surface glycoproteins and play a pivotal role in mediating cell-to-cell adhesion. Adhesion molecules are divided into four major groups, (a) integrins, (b) selectins, (c) immunoglobulin superfamily, and (d) caherins.
β Integrins are heterodimers: These are divided into α and β subunits. Depending on the substructure of the β unit, there are five families, but for convenience β1 and β2 integrins are involved in leucocyte–endothelial inter-actions. β1 integrins, also known as very late activation proteins, are so named because they appear on lymphocytes several days after antigenic stimula-tion and are composed of a common β chain (CD29) paired with a different α chain. They mediate lymphocyte and monocyte binding to the endothelium receptors called vascular adhesion mol-ecule. β2 integrins also have a common β chain (CD18), which pairs with dif-ferent α chains (CD11 a, b, c) to form a number of separate molecules. These two sets of integrins mediate strong binding of leucocytes to the endothe-lial cell while β3–β5 are concerned with binding to extracellular matrix proteins such as fibronectin and vitronectin.
a. Selectins: These molecules are com-posed of three glycoproteins and are designated by three separate prefixes: E (endothelial), P (platelet), and L (leu-cocyte). The letters denote the cells on which they were first observed. These groups of selectins bind avidly to car-bohydrate molecules on leucocytes and endothelial cells.
c. Immunoglobulin superfamily: The molecules in this family are so called because they contain a common immunoglobulin-like structure. They strengthen the interaction between the T cells and APCs. They include some of the most powerful molecules in the immune system, such as the CD4, CD8, CD2, lymphocyte function antigen (LFA-3 or CD58), and the intercellular adhesion molecules such as ICAM-1 through 3.
d. Cadherins: These molecules are calcium-dependent adhesion mole-cules and are mainly important in establishing molecular connections between epithelial cells. Their particular importance is during embryonic devel-opment.