MHCII

MHC class II molecules (MHC II or MHCII) are heterodimeric membrane proteins expressed primarily on professional antigen-presenting cells such as dendritic cells, macrophages, B cells, and thymic epithelial cells. They present peptide antigens to CD4+ T helper cells, triggering adaptive immune responses and shaping antibody production and other immune effector functions.

Structurally, MHC II consists of an alpha and a beta chain, encoded by genes in the human HLA-D region (notably HLA-DRA with various HLA-DRB genes, plus DP and DQ loci). The extracellular domains form a peptide-binding groove with open ends, allowing binding of longer peptides (typically around 12–25 amino acids). The region is highly polymorphic, contributing to diverse peptide presentation among individuals. Expression of MHC II is upregulated by the master regulator CIITA and can be induced by cytokines such as interferon-gamma.

Antigen processing for MHC II begins with the uptake of extracellular proteins into endosomes/lysosomes, where proteins are degraded into peptides. In the endoplasmic reticulum, the invariant chain (Ii, CD74) blocks the binding groove and directs trafficking of MHC II to peptide-loading compartments. After Ii is degraded to a CLIP peptide, HLA-DM facilitates exchange for higher-affinity peptides, yielding peptide–MHC II complexes that are transported to the cell surface for recognition by CD4+ T cell receptors.

Functionally, MHC II presentation is essential for CD4+ T cell activation, providing help to B cells for antibody production and to macrophages and other cells for coordination of immune responses. Polymorphisms in MHC II genes are associated with autoimmune disease risk and transplant compatibility.