MICA (MHC class I polypeptide-related sequence A) is a critical immune regulatory protein belonging to the non-classical MHC class I family. Encoded by the MICA gene on human chromosome 6, it is typically expressed on epithelial cells, fibroblasts, and endothelial cells, with upregulated expression under stress conditions such as infection, heat shock, or malignant transformation. Structurally, MICA resembles classical MHC class I molecules, featuring 伪1, 伪2, and 伪3 extracellular domains, but unlike MHC I, it does not bind 尾2-microglobulin or present antigens. Its primary function involves interaction with the activating receptor NKG2D (Natural Killer Group 2 Member D) on NK cells and cytotoxic T cells, triggering cytotoxicity and cytokine production, thereby playing a key role in antitumor and antimicrobial immunity. Tumors often evade immune surveillance by proteolytic shedding of MICA, making it a significant target in cancer immunotherapy. MICA's high polymorphism (over 100 alleles) is also associated with autoimmune diseases and transplant rejection. Additionally, certain viruses (e.g., cytomegalovirus) encode proteins that disrupt MICA-NKG2D interactions to evade immune clearance.
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