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

MHC class I polypeptide-related sequence A (MICA) and B (MICB), collectively known as MIC stress ligands, are cell surface glycoproteins that serve as primary ligands for the activating receptor NKG2D found on natural killer (NK) cells and certain T cells. Unlike classical MHC molecules, MICA/B do not present peptides but are instead upregulated in response to cellular stressors such as DNA damage, viral infection, or malignant transformation. In the context of oncology, many tumors attempt to evade immune detection by proteolytically shedding these ligands from their surface using metalloproteinases like ADAM10 and ADAM17. This shedding results in soluble MICA/B (sMICA/B), which can systemically downregulate NKG2D expression on immune cells, leading to immunosuppression. Therapeutic strategies currently under investigation include monoclonal antibodies designed to stabilize MICA/B on the cell surface by preventing shedding, thereby restoring the immune system's ability to recognize and eliminate malignant cells.

Other names

MIC stress ligandsMHC class I-related sequence AMHC class I-related sequence BStress-induced NKG2D ligandsMIC-AMIC-B

Prevention of proteolytic shedding of MICA/B from the tumor cell surface to maintain NKG2D-mediated immune surveillance and induction of antibody-dependent cellular cytotoxicity (ADCC).