MHC Complex; Gene organization. MHC complex class I, II and III molecules.

The Major Histocompatibility Complex (MHC), also known as the Human Leukocyte Antigen (HLA) complex in humans, is a highly polymorphic region of the genome that plays a critical role in the immune system. It is located on chromosome 6 in humans (chromosome 17 in mice) and consists of several genes and gene clusters. The MHC complex is divided into three major classes: Class I, Class II, and Class III, each with distinct functions.

1. MHC Class I Molecules:

• Gene Organization: MHC Class I genes are typically found in two regions: HLA-A, HLA-B, and HLA-C, which are classical MHC Class I genes, are located in the MHC Class I gene cluster. Non-classical MHC Class I genes, such as HLA-E, HLA-F, and HLA-G, are found elsewhere in the genome.
• Function: MHC Class I molecules are expressed on the surface of most nucleated cells in the body. They present endogenous antigens, typically peptides derived from intracellular pathogens (viruses, intracellular bacteria) or self-antigens, to cytotoxic T lymphocytes (CD8+ T cells). This presentation helps the immune system identify and destroy infected or abnormal cells.

2. MHC Class II Molecules:

• Gene Organization: MHC Class II genes are primarily found in the MHC Class II gene cluster. In humans, this cluster includes HLA-DP, HLA-DQ, HLA-DR, and several other genes that encode various subunits of MHC Class II molecules.
• Function: MHC Class II molecules are expressed on the surface of antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. They present exogenous antigens, typically peptides derived from extracellular pathogens (e.g., bacteria, fungi), to helper T lymphocytes (CD4+ T cells). This presentation helps activate the adaptive immune response.

3. MHC Class III Molecules:

• Gene Organization: MHC Class III genes are found within the MHC complex but do not encode classical MHC Class I or II molecules. Instead, they include genes that encode proteins involved in the immune response and other functions. Some notable genes in the MHC Class III region include those encoding complement components (C2, C4, and factor B), cytokines (e.g., tumor necrosis factor, TNF), and heat shock proteins.
• Function: The MHC Class III genes are not directly involved in antigen presentation but play essential roles in the immune response and other cellular processes. For example, complement proteins are involved in the immune system's defense against pathogens, while cytokines regulate immune cell communication and inflammation.

The MHC complex is highly polymorphic, meaning that there are numerous allelic variations of MHC genes within the human population. This polymorphism is crucial for the immune system's ability to recognize a wide range of antigens. The specific combination of MHC alleles an individual possesses can influence their susceptibility to infections, autoimmune diseases, and transplant compatibility.