Major histocompatibility complex class II molecules (MHC class II)

Major histocompatibility complex (MHC) class II molecules are essential components of the adaptive immune system that present peptide antigens to CD4+ T cells. They are heterodimers composed of an α chain and a β chain, both encoded in the MHC gene complex, featuring an open-ended peptide-binding groove that binds longer peptides (typically 15-24 amino acid residues). MHC class II molecules are primarily expressed on professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, B cells, and thymic epithelial cells, with expression regulated by CIITA and inducible by interferon-gamma (IFN-γ). The antigen presentation pathway involves their synthesis in the endoplasmic reticulum (ER) in complex with invariant chain (Ii). This complex is then transported to late endosomal compartments where Ii is cleaved, leaving CLIP (class II-associated invariant chain peptide) bound to the groove. HLA-DM, a non-classical MHC molecule, facilitates the exchange of CLIP for higher-affinity peptides derived from proteolytically degraded exogenous proteins. The resulting peptide-MHC class II complex is then transported to the cell surface for recognition by CD4+ T cells. The primary function of MHC class II molecules is to present exogenous antigens to CD4+ T helper cells, a process crucial for initiating adaptive immune responses, coordinating effector cells, determining appropriate immune responses to pathogens, and contributing to self/non-self discrimination. In humans, classical MHC class II molecules are known as Human Leukocyte Antigens (HLAs), specifically HLA-DR, HLA-DP, and HLA-DQ, while HLA-DM and HLA-DO are non-classical molecules assisting in peptide loading. Their critical roles extend to immune surveillance, susceptibility to autoimmune diseases, transplant rejection, vaccine efficacy, and various inflammatory conditions, making them significant targets for therapeutic modulation.

Other names

Human Leukocyte AntigensHLAsHLA-DRHLA-DPHLA-DQHLA-DMHLA-DO

Modulating the binding and presentation of exogenous peptide antigens to CD4+ T cells, or interfering with the intracellular antigen processing and loading pathway.