MHC class I polypeptide-related sequence A (MICA) (MICA)

MHC class I polypeptide-related sequence A (MICA) is a highly polymorphic cell surface glycoprotein that serves as a primary ligand for the activating receptor NKG2D, which is expressed on Natural Killer (NK) cells, γδ T cells, and CD8+ T cells (Bauer et al., 1999, Science, PMID: 10426993). Unlike classical MHC class I molecules, MICA does not present peptides but is instead upregulated in response to cellular stressors such as DNA damage, viral infection, or malignant transformation (Groh et al., 1996, PNAS, PMID: 8917551). In many cancers, MICA is overexpressed on the tumor cell surface, providing a signal for the immune system to identify and eliminate transformed cells. However, tumors frequently employ an evasion mechanism by proteolytically shedding MICA from the cell surface using metalloproteinases, resulting in soluble MICA (sMICA) that acts as a decoy and downregulates NKG2D expression on effector cells (Groh et al., 2002, Nature, PMID: 12192402). Therapeutic approaches targeting MICA include monoclonal antibodies like CLN-619 that stabilize surface expression or block shedding, as well as CAR-T and CAR-NK cell therapies designed to recognize MICA-expressing tumors (Ferrari de Andrade et al., 2018, Nature, PMID: 29590064). These strategies aim to restore the immune system's ability to recognize and destroy tumor cells through the NKG2D-mediated stress-sensing pathway.

Other names

MIC-AMHC class I-related chain APERB11.1Stress-induced antigenNKG2D ligand

Binding to and activation of the NKG2D receptor on Natural Killer (NK) cells and γδ T cells to trigger cytotoxic immune responses against stressed or transformed cells, or preventing the proteolytic shedding of these ligands from the tumor cell surface.