The Structure of MHC
MHC Class I
MHC Class I is a membrane spanning molecule composed of two proteins. The membrane spanning protein is approximately 350 amino acids in length, with approximately 70 amino acids at the carboxylic end comprising the transmembrane and cytoplasmic portions. The remaining 270 amino acids are divided into three globular domains labeled alpha-1, alpha-2 and alpha-3 prime, with alpha-1 being closest to the amino terminus and alpha-3 closest to the membrane. The second portion of the molecule is a small globular protein called beta-2 microglobulin. It associates primarily with the alpha-3 prime domain and is necessary for MHC stability.
 
 

MHC Class II


Though similar to class I molecules, MHC Class II is composed of two membrane spanning proteins. Each of these proteins is approximately 30 kilodaltons in size, and made of two globular domains. The domains are named alpha-1, alpha-2, beta-1 and beta-2. The two regions farthest from the membrane are alpha-1 and beta-1. The two proteins associate without covalent bonds.
 
Genetics of MHC

In humans, the MHC I and II genes are located at separate, but nearby loci on the sixth chromosome. The class I locus contains three smaller loci of genes for three distinct class I genes, named A, B and C. All code for class I molecules, but each is distinct in its structure and binding capacity.

Every human possesses at least one version of A, B and C class I molecules. Since an individual gains one strand of DNA from each parent, most people have two distinct variants of A, two of B and two of C, for a total of six distinct MHC I genes. The class I gene codes only for the alpha protein of the Class I molecule. The beta-2 microglobulin gene is very constant and is located elsewhere in the genome.

A similar situation exists for MHC II, where the locus is split into three smaller loci named DP, DQ and DR. Again, most people have two variants of each, for a total of six MHC II genes. Each gene codes for a variant of both the alpha and beta protein. Since it is possible for an alpha unit from one gene to associate with a beta of another, there are a maximum of twelve different MHC II molecules.

The prevalence of different HLA types vary widely in different populations. This variability may have as-yet undetermined effects on the efficacy of immune responses to different vaccine constructs in different genetically distinct populations.