MHC class I polypeptide-related sequence A(MICA) is a cell surface glycoprotein encoded by the MICAgene located within MHC locus. MICA is related to MHC class I and has similar domain structure, which is made up of external α1α2α3 domain, transmembrane segment and C-terminal cytoplasmic tail. However, MICA is not associated with β2-microglobulin nor binds peptides as conventional MHC class I molecules do. MICA rather functions as a stress-induced ligand for NKG2D receptor. For example, the heat shock stress pathway is involved in the regulation of MICA expression as transcription of MICA is regulated by promoter heat shock element. MICA is broadly recognized by NK cells, γδ T cells, and CD8+ αβ T cells which carry NKG2D receptor on their cell surface. As a result of NKG2D-MICA engagement, effector cytolytic responses of T cells and NK cells against epithelial tumor cells expressing MICA are initiated.
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