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

MHC class I polypeptide-related sequence A (MICA) and B (MICB) are highly polymorphic, stress-inducible cell surface glycoproteins encoded within the MHC class I region of chromosome 6[1][3]. Both act as ligands for the activating immune receptor NKG2D, which is present on the surface of natural killer cells and some cytotoxic lymphocytes[1][3][6]. Unlike classical MHC class I molecules, they do not bind peptides or associate with β2-microglobulin but instead function as "danger signals" marking stressed, infected, damaged, or transformed (including tumor) cells for immune recognition and destruction[1][3]. MICA and MICB are minimally expressed on most healthy cells but are upregulated by stress, transformation, or infection[2][6], and their aberrant or enhanced expression is common in tumors and some inflammatory or autoimmune diseases[2][6]. Shedding of MICA/MICB from the surface can downregulate NKG2D on immune effectors, allowing tumors to evade immune surveillance[6][7]. Both molecules are emerging targets for cancer immunotherapy due to their role in modulating immune surveillance, but clinical agents directly targeting these proteins remain investigational.

Other names

MICA (for MHC class I polypeptide-related sequence A)MICB (for MHC class I polypeptide-related sequence B)Major histocompatibility complex class I chain-related protein AMajor histocompatibility complex class I chain-related protein B

Ligand for NKG2D (natural killer group 2, member D) receptor: engagement activates NK and cytotoxic T cells to kill target cells expressing MICA/MICB[1][3][6]. Shedding of soluble MICA/MICB can downregulate NKG2D on immune cells, leading to immune evasion by tumors[6].