next up previous contents index
Next: Class-II Molecules Up: Major Histocompatibiliy Complex/Human Leucocyte Previous: Inheritence of MHC genes   Contents   Index


Class-I Molecules

Figure: Schematic representation of the MHC-class-I molecule. The molecule is attached to the cell membrane with most of the interesting parts on the outside of the cell. There are two main parts to the molecule; the polymorphic $\alpha$ chain and the monomorphic $\beta_2$ microglobulin. The $\beta_2$ microglobulin is non covalently bound to the $\alpha$ chain. The microglobulin plays a role in transporting the rest of the molecule to the cell surface. The gene for this portion of the molecule is found on chromosome 15. The $\alpha$ chain consists of three domains, termed $\alpha$-1,$\alpha$-2 and $\alpha$-3. All of these are similar to the Ig molecule and thus belong to the Ig superfamily of molecules. The gene that codes for the $\alpha$ chain is found on chromosome 6 in the HLA-A, HLA-B or HLA-C regions. The $\alpha$-3 domain bears a receptor for CD8, which is found on cytotoxic T cells. The $\alpha$-2 and $\alpha$-1 domains have a groove between them for binding with peptides which are always 9 amino-acids in length. The structure of the HLA-A2 molecule was described in 1987. [BSS$^+$87]
\begin{figure}\centering \includegraphics{mhcone}
\end{figure}

The class-I MHC molecules are termed HLA-A,HLA-B,HLA-C. There are also E, F, G and H, of which only A and B are thought to be important in transplantation.

MHC class-I molecules are found on the surfaces of virtually all cells. The exceptions are the cornea and neurons. Some cells express alot more than others. The are composed of a 45-kilodalton polymorphic MHC encoded heavy chain, $\alpha$, and a 12-kilodalton monomorphic chain, $\beta_2$-microglobulin. The polymorphic, MHC $\alpha$, chain is encoded on chromosome 6 and the monomorphic $\beta_2$-microglobulin encoded on chromosome 15.

The $\beta_2$-microglobulin component2binds non-covalently with the $\alpha$ chain and it is not attached to the cell. It plays a role in the assembly and transportation of the $\alpha$ chain to the cell surface.

The heavy chain bears 3 major domains, each of these bears resemblance to the Ig constant region and thus belong to the Ig superfamily. One of the domains acts as a receptor for CD-8 (on cytotoxic T cells) and the remaining two form a grove in which the antigen to be processed is carried. If there is no peptide antigen in the groove then the class-I molecule cannot be formed in a stable configuration. The amino acids in the groove are highly variable which accounts for their ability of these proteins to bind to many different antigens. There is room in the groove for a peptide of about 9 amino acids. The hypothesis is that each class-I allele may only bind a limited spectrum of peptides, all of which are 9 amino acids long. The two $\alpha$ subunits that form the groove for the peptide, also act as the main site for binding by the T-cell receptor complex.


next up previous contents index
Next: Class-II Molecules Up: Major Histocompatibiliy Complex/Human Leucocyte Previous: Inheritence of MHC genes   Contents   Index
Adrian P. Ireland