The Major Histocompatibility Complex (MHC) class I chain-related gene A (MICA) is a member of the MHC class I family, which plays a crucial role in the immune system. MICA is encoded within the human leukocyte antigen (HLA) class I region on chromosome 6 . Unlike classical HLA class I molecules, MICA does not present peptides to T cells but instead interacts with natural killer (NK) cells and certain subsets of T cells through the NKG2D receptor .
MICA is a polymorphic protein, meaning it has multiple variants within the population. It is composed of an α chain that is similar to classical HLA class I molecules but lacks the β2-microglobulin association . MICA is expressed on the surface of various cell types, including epithelial cells, fibroblasts, and endothelial cells, particularly under conditions of cellular stress, damage, or transformation .
The primary function of MICA is to act as a “stress-induced ligand” for the NKG2D receptor on NK cells and certain T cells . When cells are stressed, damaged, or transformed (e.g., during infection or tumorigenesis), MICA expression is upregulated. This upregulation serves as a signal for NK cells to target and destroy the affected cells, thus playing a critical role in immune surveillance and the elimination of potentially harmful cells .
MICA has been extensively studied in the context of organ transplantation, cancer, and autoimmune diseases. In transplantation, the presence of antibodies against MICA has been associated with graft rejection and reduced graft survival . In cancer, MICA expression on tumor cells can make them more susceptible to NK cell-mediated lysis, making it a potential target for immunotherapy . Additionally, soluble forms of MICA (sMICA) can be released into the bloodstream, where they may interfere with NK cell function and contribute to immune evasion by tumors .
Recombinant MICA (rMICA) refers to the MICA protein produced through recombinant DNA technology. This involves inserting the MICA gene into an expression system, such as bacteria or mammalian cells, to produce the protein in large quantities. Recombinant MICA is used in research to study its structure, function, and interactions with other molecules. It is also being explored as a potential therapeutic agent in cancer immunotherapy .