Major Histocompatibility Complex
More than One Class of MHC
There are two major classes of MHC molecules, both of which consist of an a and a b chain, but from different sources. MHC class I molecules (MHC I) consist of one membrane-spanning a chain (heavy chain) produced by MHC genes, and one b chain (light chain or b2-microglobulin) produced by the b2-microglobulin gene. MHC class II molecules (MHC II) consist of two membrane-spanning chains, a and b, of similar size and both produced by MHC genes. In each case, the MHC molecule has a groove that binds a peptide, which it can then present at the cell surface to a T cell to elicit an immune response, because T cells only recognise antigens as complexes with MHC molecules. The two classes of MHC proteins differ not only in their structure, but more importantly in their functional roles within the immune system: the two types of MHC molecules are specialised to present different types of antigens, thereby eliciting different responses.
MHC class I
MHC I glycoproteins are present on almost every cell in the body, acting to present endogenous antigens that originate from the cytoplasm. These antigens include not only self-proteins, but also foreign proteins produced within the cell, such as viral proteins that take over the cell’s machinery in order to replicate the virus. When these proteins become degraded, the peptide fragments can be transported to the endoplasmic reticulum, where they can bind to MHC I proteins, before being transported via the Golgi apparatus to the cell surface. Once at the cell surface, the membrane-bound MHC I protein displays the antigen for recognition by special immune cells known as cytotoxic T cell lymphocytes. MHC I proteins work to present the types of proteins being synthesised within a cell, which can then be monitored by killer T cells as part of a surveillance system that identifies and destroys any cell with over-abundant or unfamiliar peptide antigens, such as malignant cells or those harbouring viruses.
MHC class II
MHC II glycoproteins are only present on specialised antigen-presenting immune cells, including macrophages that engulf foreign particles such as bacteria, dendritic cells that present antigen to T cells, and B cells that produce antibodies. MHC II proteins present exogenous antigens that originate extracellularly from foreign bodies such as bacteria. Upon encountering a pathogenic organism, proteins from the pathogen can be degraded into peptide fragments by the antigen-presenting cell, which then sequesters these fragments into the endosome so they can bind to MHC II proteins, before being transported to the cell surface. Once at the cell surface, the membrane-bound MHC II protein displays the antigen for recognition by a different type of T cell, namely the helper T cell lymphocyte. These helper T cells are activated upon binding to macrophage or dendritic cell MHC II-antigen, causing the release of lymphokines that attract other cells to the area of infection in an attempt to confine and destroy the antigenic material. In addition, the binding of helper T cells to B cell MHC II-antigen stimulates the development of a clone of antibody-producing cells against the antigenic material.
Major differences between MHC classes I and II
|
MHC class I |
MHC class II |
|
Comprised of an MHC-encoded a chain and a b2-microglobulin chain |
Comprised of MHC-encoded a and b chains |
|
Present
on most cells |
Present
only on antigen-presenting cells |
|
Bind
endogenous antigens synthesized in a cell |
Binds exogenous
antigens |
|
Present antigen to cytotoxic T cell lymphocytes |
Present antigen to helper T cell lymphocytes |
|
Bind CD8 adhesion molecules on cytotoxic T cells |
Bind CD4 adhesion molecules on helper T cells |
|
Presence of foreign or over-abundant antigens targets cell for destruction |
Presence of foreign antigens induces antibody production, and attracts immune cells to area of infection |