MHCIIKomplex

MHCIIKomplex, commonly called MHC class II (MHC II), is a cell-surface protein complex that presents peptides derived from extracellular proteins to CD4+ T helper cells. In humans, MHC II molecules are encoded by the HLA-DP, HLA-DQ, and HLA-DR gene loci.

MHC II molecules are heterodimers composed of an alpha and a beta chain, with the peptide-binding groove formed by the α1 and β1 domains. They are mainly expressed on professional antigen-presenting cells—dendritic cells, macrophages, and B cells—but can be induced on other cells by inflammatory cytokines such as interferon-γ.

In the endoplasmic reticulum, the invariant chain (CD74) binds MHC II, blocking premature peptide binding and directing the complex to endosomal/lysosomal compartments. In these compartments, the CLIP peptide occupies the groove until HLA-DM facilitates exchange for an antigenic peptide, after which MHC II–peptide complexes reach the cell surface.

On the cell surface, the MHC II–peptide complex is recognized by CD4+ T cell receptors, activating helper T cells and triggering cytokine production. This response supports B cell antibody production and macrophage activation, forming a central component of adaptive immunity against extracellular pathogens.

Genetic variation in HLA-DP, -DQ, and -DR shapes the peptide repertoire and influences susceptibility to autoimmune diseases and transplant outcomes. Regulation of MHC II expression is enhanced by IFN-γ; aberrant expression can occur in inflammation, autoimmunity, or certain tumors.