Antigen presentation by MHC class II
Antigen processing and presentation is the process by which antigen-presenting cells express antigen on cell surface in a form recognizable by lymphocytes. Antigen processing consists of protein fragmentation (proteolysis), association of fragments with MHC (major histocompatibility complex) and expression of peptide-MHC complex at cell surface where they can be recognized by T cell receptor ( TCR ).
Expression of MHC genes is constitutively activated during development in professional antigen-presenting cells, such as B cells, dendritic cells, and macrophages.
There are two classes of MHC molecules, MHC class I and MHC class II. MHC class II proteins specialize in presentation of exogenous antigens to TCR of CD4+ T-cells.
Exogenous proteins are endocytosed and degraded by acidic proteases ( Legumain, Cathepsin L and Cathepsin S ) resident within endosomes and lysosomes . Gamma-interferon-inducible lysosomal thiol reductase IP-30 facilitates unfolding of endocytosed antigens in MHC class II -containing compartments by enzymatic cleavage of disulfide bonds .
MHC class II molecules are assembled in the endoplasmic reticulum by the chaperone CD74, which directs these complexes to the endosomal compartments. Processing of CD74 includes its initial cleavage by Legumain, followed by late stage cleavage by Cathepsin S and Cathepsin L , .
HLA-DM, a vesicle membrane protein, mediates CD74 removal (its last small fragment) from MHC class II polypeptides, and then MHC class II molecules are capable to bind antigens. MHC class II - Antigen complex is then transported to cell surface for presentation to CD4+ T-cells .