Beta-2 microglobulin

Structure and function

β₂ microglobulin lies beside the α₃ chain on the cell surface. Unlike α₃, β₂ has no transmembrane region. Directly above β₂ (that is, further away from the cell) lies the α₁ chain, which itself is next to the α₂.

β₂ microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 (5 genes in humans), MR1, the neonatal Fc receptor (FcRn), and Qa-1 (a form of alloantigen). Nevertheless, the β₂ microglobulin gene is outside of the MHC (HLA) locus, on a different chromosome.

An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporter ferroportin on the basolateral membrane of enterocytes and cell membrane of macrophages for degradation resulting in decreased iron uptake from food and decreased iron release from recycled red blood cells in the MPS (mononuclear phagocyte system) respectively. Loss of this function causes iron excess and hemochromatosis.

In a cytomegalovirus infection, a viral protein binds to β₂ microglobulin, preventing assembly of MHC class I molecules and their transport to the plasma membrane.

Mice models deficient for the β₂ microglobulin gene have been engineered. These mice demonstrate that β₂ microglobulin is necessary for cell surface expression of MHC class I and stability of the peptide-binding groove. In fact, in the absence of β₂ microglobulin, very limited amounts of MHC class I (classical and non-classical) molecules can be detected on the surface (bare lymphocyte syndrome or BLS). In the absence of MHC class I, CD8⁺ T cells cannot develop. (CD8⁺ T cells are a subset of T cells involved in the development of acquired immunity.)