Genetics, Human Major Histocompatibility Complex (MHC)

Excerpt

The HLA (human leukocyte antigens) complex is located on the short arm of chromosome 6. The HLA genes follow the principles of Mendelian genetics and the encoded antigens are co-dominantly expressed on the cell surface. In the absence of a recombination event, HLA genes are normally inherited en bloc from each parent due to their close proximity resulting in their close physical linkage. The HLA haplotype is a combination of linked HLA genes (HLA-A, -B,-C,-DR, -DQ,-DP) transmitted on a single parental chromosome. HLA antigens are expressed on the surface of many cells and play a major role in self-recognition, evoking the immune response to an antigenic stimulus, and to the orchestration of cellular and humoral immunity. HLA complex is known to be highly polygenic as it is composed of many genes, which can divide broadly into three categories: Class I, Class II, and Class III. Polymorphism is another feature of the HLA molecule. Polymorphism allows the presence of multiple variations of antigens or alleles. The HLA class I and class II antigens have the most highly polymorphic structural genes found in humans, which allows amino acids in any given HLA molecule to vary slightly from one person to the next. This variation generates distinct HLA types and also causes allograft rejection when tissues are transplanted.