ADHESION MOLECULES
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.
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