MHC Class I

By Victoria Osinski, PhD

The major histocompatibility complex (MHC) is responsible for binding peptide fragments arising from pathogens in order to display them on the cell surface for recognition from immune cells.  Once recognized, the foreign pathogen is typically evaded. The MHC complex is broken into two categories, MHC Class I proteins and MHC Class II proteins.  MHC complex I and II proteins are all very different and contain specific molecules to bind different peptides – in fact, they have been described as the most polymorphic genes there are.

MHC molecules (also known as major histocompatibility complex molecules) assist in the presentation of antigens to T cells in order to eradicate foreign pathogens.  These molecules are highly polymorphic, meaning that they exist in multiple variants in order to avoid pathogens evading their activation of the immune response.  MHC Class I molecules in particular deliver cytosolic peptides to the cell surface so that they can continue on through the cytosol and ultimately the endoplasmic reticulum (ER).

The products of MHC genes are antigen-presenting molecules (APMs) designed for antigen fragment (peptide) presentation to the T-cell receptor. In particular, MHC Class I molecules play a key role in the immune system by presenting endogenously synthesized peptides derived from the endoplasmic reticulum (ER) lumen to CD8+ T-lymphocytes, which are usually cytotoxic T-cells. MHC Class I antigens are heterodimers consisting of one 44kD highly polymorphic alpha chain non-covalently complexed with an invariant 11.5kD beta2-microglobulin subunit.