MHC II

MHC II molecules are heterodimeric glycoproteins (alpha and beta chains) that present peptides derived from extracellular/exogenous proteins that have been phagocytosed or endocytosed and processed in the endolysosomal pathway. The invariant chain initially occupies the peptide-binding groove and is later cleaved, with HLA-DM catalyzing exchange of the CLIP fragment for antigenic peptide. The peptide-MHC II complex is then presented on the cell surface for recognition by the T cell receptor (TCR) of CD4+ T helper cells, with CD4 co-receptor binding to the invariant portion of MHC II. This interaction, along with costimulatory signals (e.g., B7-CD28), leads to helper T cell activation, which is critical for B cell antibody class switching, macrophage activation, and cytotoxic T cell responses. MHC II is encoded by HLA-DR, HLA-DQ, and HLA-DP genes on chromosome 6 in humans, and expression can be upregulated by interferon-gamma. Clinically, specific HLA-DR alleles are associated with autoimmune diseases (e.g., HLA-DR3 with Graves disease, SLE, and type 1 diabetes; HLA-DR4 with rheumatoid arthritis and type 1 diabetes; HLA-DR2 with multiple sclerosis and Goodpasture syndrome). Bare lymphocyte syndrome type II is a rare immunodeficiency caused by defective MHC II expression, leading to absent CD4+ T cells and severe combined immunodeficiency-like presentation. Understanding MHC II is essential for grasping antigen presentation, T cell selection in the thymus, transplant rejection, and autoimmune disease associations.