MICA (MHC class I chain-related molecule A) is a stress-inducible glycoprotein belonging to the non-classical MHC class I family. It is encoded within the major histocompatibility complex (MHC) region and expressed on epithelial cells, fibroblasts, and endothelial cells, particularly under cellular stress, viral infection, or malignant transformation. MICA interacts with the activating receptor NKG2D on natural killer (NK) cells, γδ T cells, and CD8+ αβ T cells, triggering cytotoxic responses against stressed or infected cells.
MICA antibodies arise in contexts where immune recognition of MICA is disrupted. In organ transplantation, MICA mismatches between donor and recipient can induce alloantibodies, contributing to graft rejection and vasculopathy. These antibodies may activate endothelial cells via complement-dependent pathways or antibody-mediated cellular cytotoxicity. In autoimmune diseases, abnormal MICA expression on tissues may promote autoantibody production. In cancer, tumor cells often shed soluble MICA (sMICA) to evade NKG2D-mediated immune surveillance. Anti-MICA antibodies might neutralize sMICA, restoring antitumor immunity, though their role remains controversial.
MICA's extensive polymorphism (>100 alleles) complicates antibody detection and clinical interpretation. Research focuses on understanding MICA antibody pathogenicity, diagnostic utility in transplant monitoring, and therapeutic potential in cancer immunotherapy. Challenges include standardizing detection assays and clarifying mechanisms linking MICA antibodies to disease progression or protection.