MHC

The Major Histocompatiblity Complex (MHC) was originally discovered as a system of surface antigens significant in transplant organ rejection. Therefore, the serologically defined antigens were termed transplantation antigens or human leukocyte antigens (HLA). MHC class I and class II molecules have different structures.

The proteins encoded in the major histocompatibility complex occur on the surface of all nucleated cells of vertebrates. The coding MHC genes are found in humans (except for the gene localized on chromosome 15, which codes for beta2-microglobulin) on the short arm of chromosome 6.

The MHC complex is divided into 3 classes:

• MHC class I antigens are found on the surface of all nucleated cells of the organism and are used for antigen presentation to CD8+ T cells. They consist of a larger subunit anchored to the cell membrane, the heavy chain, and a smaller soluble unit, the beta2-microglobulin, as well as an antigenic peptide. Infected and neoplastic cells that produce abnormal proteins due to infection or mutation are specifically identified and subsequently eliminated by CD8+T cells via the MHC class I pathway.
• MHC class II complex: CD4+T cells can stimulate the production of specific antibodies and the activity of phagocytes via the MHC class II pathway. MHC class II complexes are presented by(professional) antigenpresenting cells(APC) and recognized by receptors of T helper cells (CD4+ T cells). APCs include monocytes and macrophages, interdigitating dendritic cells in the epidermis(Langerhans cells), lymph nodes and other tissues, phagocytosis-active cells of the vascular endothelium and B lymphocytes.
• MHC class III complex: This is a collective term for genes with different functions that are localized between the class I and class II genes on chromosome 6 in humans. These include complement genes, genes from cortisol synthesis as well as genes of the heat shock 70 family and tumor necrosis factor (see below tumor necrosis factor-alpha)

Both the MHC-I and MHC-II complexes exhibit a large allelic polymorphism, which is particularly pronounced in the region of the peptide binding sites. The different alleles result in an enormous expansion of the possibilities to specifically bind peptides. This, together with the diversity of TCR specificities, contributes to an almost unlimited diversity of adaptive immune responses.

MHC proteins are expressed on the surface of certain immunologically active cells. MHC proteins are particularly easy to detect on leukocytes. This is the origin of the name HLA system (Human Leucocyte Antigen) for the regulatory system of human immune defense, of which the MH complex is the most important component. Mutations and polymorphisms in various MHC genes lead to immunodeficiency. MHC genes lead to immunodeficiencies (see below MHC class I defect, MHC class II defect (D81.6), also called bare lymphocyte syndrome type I/II). See below Immunodeficiencies, primary - overview.