MHC class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) (MICA (for MHC class I polypeptide-related sequence A), MICB (for MHC class I polypeptide-related sequence B))

MHC class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) are structurally related, highly polymorphic cell surface glycoproteins encoded within the major histocompatibility complex (MHC) locus on chromosome 6. Unlike classical MHC class I molecules, MICA and MICB do not bind peptides or associate with β2-microglobulin. Instead, they function as stress-induced ligands for the activating immune receptor NKG2D (KLRK1), which is found on natural killer (NK) cells, CD8+ T cells, and some γδ T cells. Expression of MICA/B is induced by cellular stress, infection, or transformation (as in cancer), marking cells for destruction by cytotoxic lymphocytes. Although mainly detected on the surface of tumor and infected cells, low levels and mostly intracellular localization of MICA/B are found in various normal tissues. Their interaction with NKG2D is a crucial component of innate immune surveillance against tumors and infected cells. Shedding of soluble MICA/B from tumor cells can modulate immune responses and has been implicated in immune evasion in cancer[1][3][4][5][6][7][8]

Other names

MHC class I chain-related protein AMIC-AMHC class I chain-related protein BMIC-B

Drugs/antibodies may block or enhance MICA/B interaction with NKG2D, leading to enhanced immune cell activation or protection of healthy cells from immune destruction[5]