MHC class I chain-related protein A/B (MICA/B)

MHC class I chain-related proteins A and B (MICA and MICB) are highly polymorphic cell surface glycoproteins encoded within the major histocompatibility complex locus. Unlike classical MHC class I molecules, they do not associate with β2-microglobulin nor present peptides. Instead, they function primarily as stress-induced ligands that activate immune responses by binding to the NKG2D receptor on natural killer cells, γδ T cells, and CD8+ αβ T cells. This interaction serves as a "kill me" signal to cytotoxic lymphocytes when a cell is under stress due to infection or transformation. While their expression is upregulated in many tumor types—making them potential targets for cancer immunotherapy—they are also expressed intracellularly in most normal epithelial tissues with only occasional cell surface localization. This broad tissue distribution presents challenges for selective therapeutic targeting[3][5][6].

Other names

MICAMICBMHC class I polypeptide–related sequence A (for MICA)Major histocompatibility complex class I chain-related protein A and BStress-induced ligand for NKG2D receptor