MHC Molecules- Definition, Properties, Class, Types, Pathways


The major histocompatibility complex (MHC) is a group of genes that encode proteins that play a crucial role in the immune system. These proteins are called MHC molecules or transplantation antigens, because they are responsible for the rejection or acceptance of transplanted organs or tissues between individuals. MHC molecules are also involved in the recognition and presentation of foreign antigens to T cells, which are a type of white blood cells that mediate cellular immunity.

MHC molecules are glycoproteins that are embedded in the plasma membrane of various cells. They have two main functions:

  • To bind and display peptide fragments derived from the degradation of proteins inside or outside the cell. These peptides can be self-peptides (from the host cell) or non-self-peptides (from pathogens or foreign substances).
  • To interact with T cell receptors (TCRs) on the surface of T cells and co-receptors (CD4 or CD8) that determine the type and function of T cells. The binding of MHC molecules and TCRs triggers an immune response against the source of the peptide.

There are two main types of MHC molecules: class I and class II. Class I MHC molecules are expressed on almost all nucleated cells and present endogenous peptides (from inside the cell) to cytotoxic T cells (CD8+ T cells) that can kill infected or abnormal cells. Class II MHC molecules are expressed mainly on antigen-presenting cells (APCs), such as macrophages, dendritic cells, and B cells, and present exogenous peptides (from outside the cell) to helper T cells (CD4+ T cells) that can activate other immune cells and produce cytokines.

In humans, the MHC genes are located on chromosome 6 and are also known as human leukocyte antigens (HLA). The HLA genes are divided into three classes: class I, class II, and class III. Class I and class II genes encode the α and β chains of class I and class II MHC molecules, respectively. Class III genes encode other proteins involved in immune functions, such as complement components and inflammatory cytokines.

The HLA genes are highly polymorphic, meaning that there are many different alleles (variants) for each gene in the population. This results in a great diversity of MHC molecules that can bind and present different peptides to T cells. The polymorphism of HLA genes is also important for transplant compatibility, as matching HLA types between donor and recipient can reduce the risk of rejection.

The HLA genes are inherited as a block or a haplotype from each parent, meaning that each individual has two sets of HLA genes (one from each parent). The haplotypes are usually conserved within families or ethnic groups, but can vary widely between different populations. The haplotypes can also influence the susceptibility or resistance to certain diseases, as some HLA alleles may confer protection or predisposition to certain pathogens or autoimmune disorders.

The structure of MHC molecules consists of two domains: a peptide-binding domain and an immunoglobulin-like domain. The peptide-binding domain is formed by two α helices on top of a β sheet that create a groove or a cleft where the peptide binds. The immunoglobulin-like domain is involved in the interaction with TCRs and co-receptors. The structure of class I and class II MHC molecules differs in the number and origin of their chains, the size and shape of their peptide-binding groove, and their distribution and expression on different cell types.

The function of MHC molecules is to present peptides to T cells in a specific and restricted manner. This means that T cells can only recognize peptides that are bound to self-MHC molecules (MHC restriction) and that match their TCR specificity (antigen specificity). This ensures that T cells can distinguish between self and non-self antigens and mount an appropriate immune response against foreign invaders or abnormal cells.