Class-II Molecules

Figure: Schematic representation of the MHC-class-II molecule. The molecule is attached to the cell membrane with most of the interesting parts on the outside of the cell. The molecule is a heterodimer of polymorphic $\alpha$ and $\beta$ chains. Both $\alpha$ and $\beta$ chains consists of two domains, termed $\alpha$-1,$\alpha$-2 and $\beta$-1, $\beta$-2. All of these are similar to the Ig molecule and thus belong to the Ig superfamily of molecules. Both chains are encoded in the HLA-DQ, HLA-DP and HLA-DR regions of chromosome 6. The $\beta$-2 domain bears a receptor for CD4, which is found on helper T cells. The $\alpha$-1 and $\beta$-1 domains have a groove between them for binding with peptides which are always 12-20 amino-acids in length.

The class-II MHC molecules are termed HLA-DQ,DP and DR. Only the DR genes are felt to be of clinical importance in transplantation.

In the class-II region are also found the TAP1 and TAP2 genes whose combined product, a protease, controls the intracellular formation and subsequent expression of MHC molecules on the cell surface. [KPK$^+$92]

In contrast to the class-I molecules which are expressed on virtually all cells, class-II molecules expression is restricted. In the main class-II molecules are expressed on the surface of antigen presenting cells. They are found on non-resting T lymphocytes and on capillary endothelial cells.

Interferon-$\gamma$ and other pro-inflammatory cytokines may bind to the promoter region of the class-II genes and initiate transcription.

The class-II molecule is composed of two MHC-encoded and non-covalently associated polymorphic chains, $\alpha$ and $\beta$. Each of these is composed of two extracellular domaines. There is a polymorphic groove for binding small peptides which fits a peptide of length 12 amino-acids. The other domain on the $\beta$ chain is a receptor for CD4 (on helper T lymphocytes).

Class-II molecules play a central role in the initiation of the immune response to transplantation antigens. Recognition of foreign class-II molecules activates helper CD4 T cells which then begin the process of clonal expansion and releasing cytokines that stimulate the clonal expansion of cytotoxic T cells.