MHC I and MHC II

Major Histocompatibility Complex: MHC I and MHC II Molecules

• Major Histocompatibility Complex (MHC) genes code for MHC molecules found on all nucleated cells of the body except mature red blood cells.
• MHC I and MHC II molecules are involved in adaptive immunity.
• MHC I molecules present self and non-self pathogen antigens to effector T cells for cellular immunity, whereas MHC II molecules present non-self pathogen antigens for initial T cell activation.
• MHC I molecules are composed of a longer α protein chain and a smaller β2 microglobulin protein; only the α chain spans the cytoplasmic membrane. MHC II molecules are composed of two protein chains, α and β, which are approximately similar in length.
• Both MHC I and MHC II molecules have a cleft that serves as the antigen-binding site near the outermost portion of the dimer.
• The antigen-binding cleft for MHC I is formed by the α1 and α2 domains, whereas for MHC II, the cleft is formed by the α1 and β1 domains.
• MHC II molecules are found only on the surface of antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B cells.
• After dendritic cells recognize and attach to a pathogen cell, the pathogen is internalized by phagocytosis and is initially contained within a phagosome.
• Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome, where degradation of the pathogen for antigen processing begins.
• Only protein antigen epitopes are presented to T cells by MHC II, and only a selection of the most antigenic or immunodominant epitopes are presented by APCs.
• The mechanism by which epitopes are selected for processing and presentation by an APC is complicated and not well understood.
• Once the most antigenic, immunodominant epitopes have been processed, they associate within the antigen-binding cleft of MHC II molecules and are translocated to the cell surface of the dendritic cell for presentation to T cells.